Publications by authors named "Dario Didona"

80 Publications

Three novel pathogenic NEK9 variants in patients with nevus comedonicus: a case series.

J Am Acad Dermatol 2021 Apr 2. Epub 2021 Apr 2.

Institute of Human Genetics, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2021.03.096DOI Listing
April 2021

Cutaneous Squamous Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Biomedicines 2021 Feb 9;9(2). Epub 2021 Feb 9.

IDI-IRCCS, Dermatological Research Hospital, via di Monti di Creta 104, 00167 Rome, Italy.

Cutaneous squamous cell carcinoma (cSCC), a non-melanoma skin cancer, is a keratinocyte carcinoma representing one of the most common cancers with an increasing incidence. cSCC could be in situ (e.g., Bowen's disease) or an invasive form. A significant cSCC risk factor is advanced age, together with cumulative sun exposure, fair skin, prolonged immunosuppression, and previous skin cancer diagnoses. Although most cSCCs can be treated by surgery, a fraction of them recur and metastasize, leading to death. cSCC could arise de novo or be the result of a progression of the actinic keratosis, an in situ carcinoma. The multistage process of cSCC development and progression is characterized by mutations in the genes involved in epidermal homeostasis and by several alterations, such as epigenetic modifications, viral infections, or microenvironmental changes. Thus, cSCC development is a gradual process with several histological- and pathological-defined stages. Dermoscopy and reflectance confocal microscopy enhanced the diagnostic accuracy of cSCC. Surgical excision is the first-line treatment for invasive cSCC. Moreover, radiotherapy may be considered as a primary treatment in patients not candidates for surgery. Extensive studies of cSCC pathogenic mechanisms identified several pharmaceutical targets and allowed the development of new systemic therapies, including immunotherapy with immune checkpoint inhibitors, such as Cemiplimab, and epidermal growth factor receptor inhibitors for metastatic and locally advanced cSCC. Furthermore, the implementation of prevention measures has been useful in patient management.
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http://dx.doi.org/10.3390/biomedicines9020171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7916193PMC
February 2021

Immunophenotyping in pemphigus reveals a T17/T17 cell-dominated immune response promoting desmoglein1/3-specific autoantibody production.

J Allergy Clin Immunol 2020 Nov 20. Epub 2020 Nov 20.

Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany.

Background: T2 cells were thought to be a pivotal factor for initiation of the autoimmune blistering disease pemphigus. However, the role of other T-cell subsets in pemphigus pathogenesis remained unclear.

Objective: We aimed to characterize the exact phenotype of T cells responsible for the development of pemphigus.

Methods: Whole transcriptome shotgun sequencing was performed to determine differential gene expression in pemphigus lesions and skin of healthy individuals. The cutaneous cytokine signature was further evaluated by real-time quantitative PCR. In peripheral blood, the distribution of T cell and folliclular helper (T) cell subsets was analyzed by flow cytometry. Finally, the capacity of T and T cell subsets to induce desmoglein (Dsg)-specific autoantibodies by memory B cells was evaluated in coculture experiments.

Results: Transcriptome analysis of skin samples identified an IL-17A-dominated immune signature in patients with pemphigus, and Kyoto Encyclopedia of Genes and Genomes pathway analysis confirmed the dominance of the IL-17A signaling pathway. Increased expression of IL17A and associated cytokines was also detected by real-time quantitative PCR comparing lesional with perilesional or healthy skin. Interestingly, utilization of flow cytometry showed that patients with active pemphigus had elevated levels of circulating IL-17 T17, T17, and T17.1 cells. Notably, levels of T17 and T17 cells correlated with levels of Dsg-specific CD19CD27 memory B cells, and patients with acute pemphigus showed higher levels of Dsg3-autoreactive T17 cells. Coculture experiments revealed T17 cells as primarily responsible for inducing Dsg-specific autoantibody production by B cells.

Conclusion: Our findings show that T17 cells are critically involved in the pathogenesis of pemphigus and offer novel targets for therapeutic intervention.
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http://dx.doi.org/10.1016/j.jaci.2020.11.008DOI Listing
November 2020

Basal Cell Carcinoma: From Pathophysiology to Novel Therapeutic Approaches.

Biomedicines 2020 Oct 23;8(11). Epub 2020 Oct 23.

Istituto Dermopatico dell'Immacolata-IRCCS, via dei Monti di Creta 104, 00167 Rome, Italy.

Basal cell carcinoma (BCC) is the most common human cancer worldwide, and is a subtype of nonmelanoma skin cancer, characterized by a constantly increasing incidence due to an aging population and widespread sun exposure. Although the mortality from BCC is negligible, this tumor can be associated with significant morbidity and cost. This review presents a literature overview of BCC from pathophysiology to novel therapeutic approaches. Several histopathological BCC subtypes with different prognostic values have been described. Dermoscopy and, more recently, reflectance confocal microscopy have largely improved BCC diagnosis. Although surgery is the first-line treatment for localized BCC, other nonsurgical local treatment options are available. BCC pathogenesis depends on the interaction between environmental and genetic characteristics of the patient. Specifically, an aberrant activation of Hedgehog signaling pathway is implicated in its pathogenesis. Notably, Hedgehog signaling inhibitors, such as vismodegib and sonidegib, are successfully used as targeted treatment for advanced or metastatic BCC. Furthermore, the implementation of prevention measures has demonstrated to be useful in the patient management.
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http://dx.doi.org/10.3390/biomedicines8110449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690754PMC
October 2020

Paraneoplastic autoimmune multiorgan syndrome (PAMS).

G Ital Dermatol Venereol 2020 Oct 16. Epub 2020 Oct 16.

Department of Dermatology, Rouen University Hospital and INSERM U905, Centre de Référence des Maladies Bulleuses Autoimmunes, Normandie University, Rouen, France.

Originally described by Anhalt as paraneoplastic pemphigus in 1990, paraneoplastic autoimmune multiorgan syndrome (PAMS) is a potentially lethal blistering disease, characterized by polymorphous clinical features, including mucocutaneous erosions, blisters, lichenoid papules, and erythema. Several autoantibodies have been detected in serum of PAMS patients, including anti-plakins, anti-alpha-2-macroglobulin like 1, and anti-desmogleins autoantibodies. The mortality rate of PAMS is up to 50%. This is due on the one hand to the poor response to treatments and on the other hand to the delay in the diagnosis and to the prognosis of the underlying neoplasia.
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http://dx.doi.org/10.23736/S0392-0488.20.06675-4DOI Listing
October 2020

A new case series on etanercept treatment for toxic epidermal necrolysis.

Eur J Dermatol 2020 Oct;30(5):561-568

First Dermatology Division, IDI-IRCCS, FLMM, Roma, Italy.

Background: Toxic epidermal necrolysis (TEN) is a severe, potentially lethal drug reaction for which no standard treatment is available.

Objective: To describe 17 consecutive TEN patients treated with a single dose of etanercept, a TNF-alpha inhibitor.

Materials & Methods: Comorbidities and any drug treatment initiated within the previous month were recorded on admission. Patients received 50 mg etanercept in a single subcutaneous injection. The clinical severity of the disease was computed using the SCORTEN scale. The expected number of deaths was calculated based on the probability of death associated with each SCORTEN score level. Healing was defined as complete re-epithelialization. Time to healing was analysed using the Kaplan-Meier estimator.

Results: The lowest SCORTEN score was 2, and seven patients scored in the most severe risk category (i.e., =>5). A comparison between observed (2/17) vs. expected deaths (10/17) was statistically significant (p=0.012). Fifteen patients promptly responded to treatment and achieved complete re-epithelization (median time to healing: 8.5 days), without complications or side effects. The two observed deaths were due to other causes, although re-epithelization had initiated in both patients.

Conclusion: These preliminary results add to our initial observations indicating that etanercept may effectively control TEN, a potentially lethal skin condition for which there is currently no effective cure. Where funding is available, randomized controlled trials on etanercept for TEN should be conducted.
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http://dx.doi.org/10.1684/ejd.2020.3883DOI Listing
October 2020

Erythromycin-induced pemphigus foliaceus successfully treated with etanercept.

Dermatol Ther 2020 11 11;33(6):e14201. Epub 2020 Sep 11.

Department of Dermatology, Istituto Dermopatico dell'Immacolata (IDI)-IRCCS, Rome, Italy.

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http://dx.doi.org/10.1111/dth.14201DOI Listing
November 2020

Bullous pemphigoid in elderly woman affected by non-small cell lung cancer treated with pembrolizumab: A case report and review of literature.

J Oncol Pharm Pract 2021 Apr 9;27(3):727-733. Epub 2020 Aug 9.

Rare Diseases Unit, IDI-IRCCS, Rome, Italy.

Introduction: Immunotherapy has changed the management of patients with various types of malignancies (melanoma, renal, lung, and bladder cancers) but immune checkpoint inhibitors may be associated with several adverse events. Up to 20% of patients treated with immune checkpoint inhibitors may develop dermatological immune-related adverse events, mostly rashes and pruritus but rarely even bullous pemphigoid.

Case Report: We report a case of an elderly patient with advanced non-small cell lung cancer in therapy with pembrolizumab, 200 mg/body every three weeks. After 26 cycles of therapy, the patient developed widespread itching and then after 28 cycles she developed strained blisters filled with serous fluids on predominantly erythematous skin with suspicious of bullous pemphigoid. Skin biopsy confirms bullous pemphigoid, so we decided to permanently discontinue therapy with pembrolizumab and the patient is currently on therapy with doxycycline, nicotinamide, and clobetasol propionate with good regression of symptoms and cutaneous lesions.

Discussion: In the literature, the first case of bullous pemphigoid induced by pembrolizumab has been described in 2015. On Pubmed, from 2015 to date, we have found 19 cases of bullous pemphigoid during pembrolizumab therapy but only three of them are related to non-small cell lung cancer, adding our patient we reach a total of 20 cases. It could be interesting to investigate if there is a specific relationship between the appearance of itching and the development of bullous pemphigoid.
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http://dx.doi.org/10.1177/1078155220946370DOI Listing
April 2021

Clinicopathological and dermoscopic features of amelanotic and hypomelanotic melanoma: a retrospective multicentric study.

Int J Dermatol 2020 Nov 29;59(11):1371-1380. Epub 2020 Jul 29.

Unit of Dermatology, IRCCS Ospedale San Raffaele, Milan, Italy.

Background: Amelanotic and hypomelanotic melanoma (AHM) has a higher risk of delayed diagnosis and a significant lower 5-year melanoma-specific survival compared to pigmented melanoma. Our aim was the evaluation of the clinicopathological/dermoscopic features of amelanotic melanoma (AM) and hypomelanotic melanoma (HM).

Methods: All participants had a personal history of AHM. We defined HM as showing clinical/dermoscopic pigmentation in < 25% of the lesion's surface and histopathological focal pigmentation, while AM as melanomas with clinical/dermoscopic and histopathological absence of pigmentation.

Results: The most common phenotypic traits among the 145 AHM patients were as follows: phototype II, blue-grey eyes, and dark brown hair. Red hair was present in 23.8% AHM cases (AM = 22.60%; HM = 25.80%). The most affected area was the back (29.5%). A total of 67.1% were classified as AM and 32.9% as HM. The most represented hair colors in AM and HM were, respectively, blonde and dark brown hair. Median Breslow thickness was 1.7 mm, superficial spreading melanoma (SSM) and nodular melanoma (NM) were the most represented histotypes, and mitotic rate > 1 × mm was reported in 73.3% cases, and regression was significantly more present in HM. Dermoscopy showed high prevalence of white structureless zones (63.4%), linear looped vessels (58.8%), linear irregular vessels (50.0%), and arborizing vessels (47.2%). Multivariate logistic regression confirmed the association between the presence of pigmentation and the following: histological regression, dermoscopic globules, and arborizing vessels.

Conclusions: Predominance of red hair in AHM patients was not confirmed. AHM affects mostly intermittent sun-exposed body areas. The deeper median Breslow thickness (versus pigmented melanoma), the association of AM with the nodular histotype, and the high mitotic rate highlight the AHM's aggressiveness. HM's higher levels of regression can be explained by the presence of pigmentation, driving the underlying immune response. AHM showed a polymorphous vascular pattern and significant presence of arborizing vessels (especially HM).
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http://dx.doi.org/10.1111/ijd.15064DOI Listing
November 2020

Amyopathic and anti-TIF1 gamma-positive dermatomyositis: analysis of a monocentric cohort and proposal to update diagnostic criteria.

Eur J Dermatol 2020 Jun;30(3):279-288

Department of Dermatology and Allergology.

Dermatomyositis (DM) is a group of autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. An amyopathic form of DM (ADM) has been described, and more recently, an anti-TIF-1 gamma-positive subtype, characterized by poikiloderma and associated with a relatively high risk of cancer. To characterise a cohort of DM patients. A cohort of 29 DM patients was followed between January 2004 and March 2019, and investigated for clinical characteristics, pathological features based on electromyography and MRI, laboratory data, and auto-antibody profile. Based on the investigations, DM was shown to be heterogeneous. However, we identified a subgroup of anti-TIF-1 gamma-positive patients who all shared heliotrope erythema. Furthermore, we observed a positive correlation between serum glutamicoxaloacetic transaminase (GOT) and creatine kinase (CK) concentrations in patients with anti-TIF-1 gamma antibodies, which is not found in patients with anti-MDA-5 antibodies. Based on the findings of this study, we propose an update of the Sontheimer et al. diagnostic criteria to improve the sensitivity of diagnosis for ADM. In addition, we describe a significant association between serum GOT and CK levels in DM patients with anti-TIF-1 gamma antibodies, and further highlight the significance of heliotrope rash as a clinical hallmark for this particular subset of patients.
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http://dx.doi.org/10.1684/ejd.2020.3766DOI Listing
June 2020

The polymorphous spectrum of dermatomyositis: classic features, newly described skin lesions, and rare variants.

Eur J Dermatol 2020 Jun;30(3):229-242

Department of Dermatology and Allergology, Philipps-University, Marburg, Germany.

Dermatomyositis belongs to a group of rare autoimmune diseases characterized by a variable degree of skin symptoms and myopathy. The clinically diagnostic hallmarks of dermatomyositis are heliotrope rash, Gottron's papules and weakness of the proximal muscles. Along with pathognomonic, characteristic, and compatible cutaneous features, several uncommon and rare skin manifestations have been reported. In addition, new skin lesions have been described in dermatomyositis patients. Furthermore, rare clinical subtypes of dermatomyositis have been reported in the literature, including Wong-type dermatomyositis, characterised by the coexistence of dermatomyositis and pityriasis rubra pilaris with hyperkeratotic, erythematous, follicular confluent papules on the back of the hands along the bony prominences. In addition, plenty of autoantibody subsets have been recently described that are related to distinct clinical features and systemic involvement, such as anti-MDA5 autoantibodies. We reviewed the English- and German-language scientific literature using the key words "dermatomyositis", "autoantibodies", and "clinical features", alone or in combination, focusing on particular cutaneous symptoms and their association with defined autoantibody profiles. Furthermore, we focused on rare subtypes of dermatomyositis, unusual clinical features, and recently described skin lesions.
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http://dx.doi.org/10.1684/ejd.2020.3761DOI Listing
June 2020

Eine Reisedermatose mit Spätfolgen: marine Kontaktdermatitis durch Korallen mit verzögerter lichenoider Reaktion.

J Dtsch Dermatol Ges 2020 May;18(5):495-497

Klinik für Dermatologie und Allergologie, Universitätsklinikum Gießen und Marburg, Philipps Universität Marburg, Marburg.

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http://dx.doi.org/10.1111/ddg.14086_gDOI Listing
May 2020

Travel-associated dermatosis with late sequelae: Coral contact dermatitis presenting with a lichenoid reaction.

J Dtsch Dermatol Ges 2020 May 20;18(5):493-495. Epub 2020 Apr 20.

Department of Dermatology and Allergology, University Medical Center of Giessen and Marburg, Philipps University, Marburg, Germany.

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http://dx.doi.org/10.1111/ddg.14086DOI Listing
May 2020

Paraneoplastic Dermatoses: A Brief General Review and an Extensive Analysis of Paraneoplastic Pemphigus and Paraneoplastic Dermatomyositis.

Int J Mol Sci 2020 Mar 21;21(6). Epub 2020 Mar 21.

Molecular and Cell Biology Laboratory, IDI-IRCCS, 00167 Rome, Italy.

Skin manifestations of systemic disease and malignancy are extremely polymorphous. Clinicians should be familiarized with paraneoplastic dermatoses in order to perform an early diagnosis of the underlying neoplasm. Lack of familiarity with cutaneous clues of internal malignancy may delay diagnosis and treatment of cancer. In this review, we described several paraneoplastic dermatoses and discussed extensively two paradigmatic ones, namely paraneoplastic pemphigus and paraneoplastic dermatomyositis.
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http://dx.doi.org/10.3390/ijms21062178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139382PMC
March 2020

A Family with Palmar and Plantar Hyperkeratosis: A Quiz.

Acta Derm Venereol 2020 Feb 27;100(4):adv00064. Epub 2020 Feb 27.

Department of Dermatology and Allergology, Philipp University, DE-35043 Marburg, Germany.

is missing (Quiz).
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http://dx.doi.org/10.2340/00015555-3419DOI Listing
February 2020

Pemphigus: Current and Future Therapeutic Strategies.

Front Immunol 2019 25;10:1418. Epub 2019 Jun 25.

Department of Dermatology and Allergology, Philipps University, Marburg, Germany.

Pemphigus encompasses a heterogeneous group of autoimmune blistering diseases, which affect both mucous membranes and the skin. The disease usually runs a chronic-relapsing course, with a potentially devastating impact on the patients' quality of life. Pemphigus pathogenesis is related to IgG autoantibodies targeting various adhesion molecules in the epidermis, including desmoglein (Dsg) 1 and 3, major components of desmosomes. The pathogenic relevance of such autoantibodies has been largely demonstrated experimentally. IgG autoantibody binding to Dsg results in loss of epidermal keratinocyte adhesion, a phenomenon referred to as acantholysis. This in turn causes intra-epidermal blistering and the clinical appearance of flaccid blisters and erosions at involved sites. Since the advent of glucocorticoids, the overall prognosis of pemphigus has largely improved. However, mortality persists elevated, since long-term use of high dose corticosteroids and adjuvant steroid-sparing immunosuppressants portend a high risk of serious adverse events, especially infections. Recently, rituximab, a chimeric anti CD20 monoclonal antibody which induces B-cell depletion, has been shown to improve patients' survival, as early rituximab use results in higher disease remission rates, long term clinical response and faster prednisone tapering compared to conventional immunosuppressive therapies, leading to its approval as a first line therapy in pemphigus. Other anti B-cell therapies targeting B-cell receptor or downstream molecules are currently tried in clinical studies. More intriguingly, a preliminary study in a preclinical mouse model of pemphigus has shown promise regarding future therapeutic application of Chimeric Autoantibody Receptor T-cells engineered using Dsg domains to selectively target autoreactive B-cells. Conversely, previous studies from our group have demonstrated that B-cell depletion in pemphigus resulted in secondary impairment of T-cell function; this may account for the observed long-term remission following B-cell recovery in rituximab treated patients. Likewise, our data support the critical role of Dsg-specific T-cell clones in orchestrating the inflammatory response and B-cell activation in pemphigus. Monitoring autoreactive T-cells in patients may indeed provide further information on the role of these cells, and would be the starting point for designating therapies aimed at restoring the lost immune tolerance against Dsg. The present review focuses on current advances, unmet challenges and future perspectives of pemphigus management.
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http://dx.doi.org/10.3389/fimmu.2019.01418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6603181PMC
October 2020

Thymoma-Associated Paraneoplastic Autoimmune Multiorgan Syndrome-From Pemphigus to Lichenoid Dermatitis.

Front Immunol 2019 21;10:1413. Epub 2019 Jun 21.

Department of Dermatology and Allergology, Philipps-University, Marburg, Germany.

Paraneoplastic autoimmune multi-organ syndrome (PAMS) is a rare clinical condition characterized by variable and heterogeneous clinical phenotypes in the presence of neoplasias which largely depend on the activation of humoral and cellular immune responses. Clinically, these patients present with a spectrum of antibody-driven pemphigus-like lesions to graft-vs.-host-disease-like exanthemas with a lichenoid inflammatory infiltrate in the skin. PAMS is occasionally associated with thymoma, in which altered immune surveillance eventually leads to multiorgan autoimmunity which often includes variable cutaneous symptoms. This disorder is associated with a profound disturbance of peripheral immune tolerance against human autoantigens. We here present a patient with relapsing thymoma who developed PAMS with several cutaneous and extracutaneous autoimmune disorders. Peripheral blood mononuclear cells (PBMC), sera, and lesional skin biopsies were obtained at different clinical disease stages. Peripheral T cell subsets were characterized phenotypically and the cytokine profile of the peripheral blood T cellular response against distinct epidermal and dermal autoantigens of the skin was analyzed by ELISpot assay. Serological screening was performed by ELISA and immunoblot analysis. Skin biopsies were subjected to immunohistochemical analysis of distinct T cell subsets. Thymoma tissue was analyzed for the presence of T regulatory cells and compared with adult thymus and indolent thymoma. In the present case, thymoma was the cause of the observed multi-organ autoimmune syndromes as its recurrence and surgical removal was associated with the relapse and regression of the cutaneous symptoms, respectively. Initially, the patient presented with two autoimmune disorders with Th2/Th1 imbalance, myasthenia gravis (MG) and pemphigus foliaceus (PF), which regressed upon immunosuppressive treatment. Months later, the patient developed a lichenoid exanthema with a Th1-dominated skin infiltrate. Further clinical evaluation revealed the recurrence of the thymoma and the lichenoid exanthema gradually regressed upon thymectomy. Our contention that T cell recognition against distinct cutaneous autoantigens, such as desmoglein 1 (Dsg1), shifted from a Th2 to a Th1-dominated immune response could not be fully substantiated as the patient was on a stringent immunosuppressive treatment regimen. We could only observe a decrease of the initially present serum IgG autoantibodies against Dsg1. Phenotypic analysis of the associated thymoma showed a lower number of T regulatory cells compared to adult thymus and indolent thymoma, suggesting that impaired thymus-derived immune surveillance had a direct impact on the outcome of the observed cutaneous autoimmune disorders.
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http://dx.doi.org/10.3389/fimmu.2019.01413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6598597PMC
October 2020

Treatment of recalcitrant squamous carcinoma in situ of penis with tapering imiquimod 5-3.75% cream.

Dermatol Ther 2019 05 22;32(3):e12904. Epub 2019 Apr 22.

Dermatology Department, Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

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http://dx.doi.org/10.1111/dth.12904DOI Listing
May 2019

Bowel-associated dermatosis arthritis syndrome and palisading neutrophilic granulomatous dermatitis as presentation of ulcerative colitis.

G Ital Dermatol Venereol 2019 Mar 29. Epub 2019 Mar 29.

Dermatology Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.19.06198-4DOI Listing
March 2019

Correlation of serum tryptase levels with total number of nevi, Breslow thickness, ulceration, and mitotic index in melanoma patients: evaluation of a promising prognostic marker.

Melanoma Res 2019 12;29(6):621-625

Dermatologic Clinic, Department of Internal Medicine and Medical Specialties, La Sapienza University of Rome.

Current evidences suggest that mast cells contribute to the proliferation and differentiation of skin melanocytes. According to these findings, we carried out an observational cross-sectional study to investigate the correlation between the total number of nevi (TN), Breslow thickness (BT), and serum tryptase (ST) levels in a cohort of 35 melanoma (MM) patients. A Mann-Whitney test was performed to compare ST values within each variable. Subsequently, the independent predictive factors were assessed by multiple logistic regression. Pearson's χ-test was chosen to detect statistically significant findings on the TN and the histopatological variables (Breslow, ulceration, and mitotic index). The TN was assessed using a dichotomous scale (≤ 10 or > 10). Patients with TN of 10 or less (3.48 vs. 6.05 ng/ml; P = 0.045), patients with a Breslow thickness of at least 1.01 mm (2.99 vs. 5.67 ng/ml; P = 0.1), and ulcerated MM (2.37 vs. 6.05 ng/ml; P < 0.001) showed lower median ST levels. Similarly, MM with mitotic index of at least 1/mm had median ST levels lower than MM with mitotic index less than 1/mm (P = 0.005). Multiple logistic regression confirmed the statistical significance for the variables ulceration, TN, and mitotic index. Pearson's χ-test showed a statistically significantly (P = 0.003) increased prevalence of MMs with a BT of at least 1.01 mm in patients with a TN of 10 or less. Patients with a TN of 10 or less also showed a higher prevalence of ulceration and mitotic index of at least 1/mm in comparison with the rest of the cohort. Our study highlights lower median ST levels in patients whose MM thickness is at least 1.01 mm; this may encourage new studies on the role of ST in MM also according to the number of nevi.
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http://dx.doi.org/10.1097/CMR.0000000000000561DOI Listing
December 2019

Isomorphic Koebner's phenomenon or isotopic wolf's phenomenon?

G Ital Dermatol Venereol 2018 Nov 9. Epub 2018 Nov 9.

Dermatology Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.06232-6DOI Listing
November 2018

Bullous pemphigoid as a further association in extensive cases of Grover disease.

G Ital Dermatol Venereol 2020 Aug 22;155(4):515-516. Epub 2018 Oct 22.

Laboratory of Dermatopathology, San Gallicano Dermatological Institute IRCCS, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.06066-2DOI Listing
August 2020

Kaposi's sarcoma lung metastastis in transplanted patient treatment response with paclitaxel and everolimus.

G Ital Dermatol Venereol 2020 Apr 18;155(2):232-234. Epub 2018 Sep 18.

Division of Pulmunology, Regina Apostolorum Hospital, Albano Laziale, Rome, Italy.

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http://dx.doi.org/10.23736/S0392-0488.18.05904-7DOI Listing
April 2020

Galli-Galli Disease Presenting as a Lentigo-like Eruption: A Further Clinical Feature in the Wide Spectrum of Reticulate Pigment Disorders.

Acta Dermatovenerol Croat 2017 Dec;25(4):300-302

Dario Didona, MD, Prima Divisione Dermatologia Istituto Dermopatico dell'Immacolata, Via dei Monti di Creta 104, 00167 Rome , Italy;

Dear Editor, Reticulate pigmentary disorders (RPD) is a term used to classify a spectrum of several acquired and congenital disorders. Different clinical features can be present, including a reticular pattern and a freckle-like pattern with hyper- or hypo-pigmented macules (1). Dowling-Degos disease (DDD), an autosomal dominant genodermatosis, is the main type of RPD (2). Clinically, DDD presents with pigmented, reticulate, flexural macules and comedo-like papules on the back and neck. Galli-Galli disease (GGD) is a very rare variant of DDD, from which is clinically indistinguishable (3). A 65-year-old Caucasian male patient presented to our Department with a 6-year history of diffuse maculopapular lesions involving the trunk and the extensor and flexor regions of the upper and lower extremities (Figure 1). These lesions were small, monomorphous, erythematous macules and papules, some covered by discrete scales. Numerous brown lentiginous macules were also observed. The patients did not present with comedo-like lesions, reticulate pigmentation, pitted acneiform facial scars, palmar pits, or nail changes. Furthermore, the oral mucosa showed no lesions. The patient's familial history was negative for dermatoses. Laboratory routine tests were all negative. Topical and oral steroids as well as systemic retinoids were unsuccessful. Therefore, a punch biopsy was performed. Histologic examination showed a digitate elongations of rete ridges, with small foci of acantholysis (Figure 2, a). The epidermis showed a finger-like projections extending into the papillary dermis with increased melanin pigment. The epidermis was atrophic above the digitate proliferations and above the acantholytic foci, where necrotic and dyskeratotic keratinocytes also were found (Figure 2, b). In the papillary dermis, a lymphohistiocytic infiltrate with perivascular distribution was detected (Figure 2, a). According to the clinical and histological findings, a final diagnosis of Galli-Galli disease with lentigo-like macular lesions was established. The patients started 25 mg/day acitretin with only partial improvement. GGD is now considered a variant of DDD, from which is clinically indistinguishable (2,3). Several differential diagnosis can be considered, including Darier's and Groover's disease (2-9) (Table 1). Because of the absence of digitate proliferation of the rete ridges and the presence of yellow or brown macules, Darier's disease can be distinguished from GGD. In our patient, the involvement of the lower legs and the presence of unusual brown, lentigo-like macules were accurately evaluated, because of the major diagnostic pitfall with an extensive kind of Grover's-like eruption with lentiginous freckling (6). However, the involvement of sun-shielded areas and the histological presence of a lentiginous elongation of rete ridges led us to a final diagnosis of GGD. Regarding the pathogenesis, the alteration of the keratine 5 gene (12q13.13) may be the main factor in GGD. In GGD, a reduced amount of functional keratin 5 impairs the structure of keratin intermediate filaments (10). As a result, the structure of the epidermis is affected, leading to alterations in desmosomes and hemidesmosomes (2). Regarding the lentigo-like pattern of our patient, the additional diffusion of lentigos over shield-sites and the absence of extreme sun exposure in the patient's history ruled out the ultraviolet radiation as the main etiopathogenetic factor. In this regard, as reported by Girard et al., lentigos could represent a post-inflammatory pigmentation of the papular acantholytic lesions (10). However, as emphasized by Coper et al. (6), the persistence of lentigos for several years would contrast with this hypothesis. It is indeed known that a failure of keratin 5 may disrupt the movement of pigment-carrying melanosomes into keratinocytes. The disruption of melanosome transport is thought to be the cause of the pigmentation abnormalities seen in DDD as well as in GGD. These aspects could explain the elongated rete ridges and the altered pigmentation clinically and pathologically observed in GGD and DDD.
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December 2017

Atrophic and Annular Scarring Alopecia of the Scalp as a Finding in Underlying Systemic Sarcoidosis.

Acta Dermatovenerol Croat 2017 Dec;25(4):298-299

Dario Didona, MD, Prima Divisione Dermatologica , Istituto Dermopatico dell'Immacolata-IRCCS, Via dei Mont di Creta 104 , 00167 Rome, Italy;

Cutaneous sarcoidosis is not an uncommon disorder, and the skin can be the sole manifestation in about 10% of patients. However, when the involved anatomical area of the cutaneous sarcoidosis is the scalp and it presents as a scarring alopecia, there is an increased risk of a systemic disease (1,2). A 79-year-old Caucasian male patient presented to our Institute with annular and painless plaques of the scalp, with variable diameter, showing a reddish and yellowish color (Figure 1, a). Furthermore, a scleroderma-like atrophy of the skin with an exposure of the underlying vasculature was present (Figure 1, b). The patient reported that these lesions began to appear 2 years ago, with a worsening in the last 6 months. He also reported a chronic cough and dyspnea. According to the patient's medical history, he was treated for tinea capitis with radiotherapy of the scalp at the age of 7, with temporary hair-loss and subsequent total re-growth. Additionally, during the last 7 years he was diagnosed with mental depression and treated accordingly. The histology revealed typical epithelioid cell granulomas without central necrosis in association with a sparse lymphocytic infiltrate. Elastosis with ectatic vessels, sclerosis, and edema was also present in the upper dermis (Figure 1, c, d) A diagnosis of cutaneous sarcoidosis of the scalp was established. Laboratory investigations, including hepatitis B and C viral serology, anti-nuclear antibodies, antibodies to extractable nuclear antigen, cardiolipin, beta2 glycoprotein immunoglobulin G antibodies, and lymphoid subsets were all in normal ranges, whereas the angiotensin converting enzyme level was 124 (range: 65-114) IU/L. The chest radiography showed diffuse interstitial nodulations with bilateral and right para-tracheal lymphadenopathies, and the histology revealed pulmonary sarcoidosis (Figure 2). As of this writing, the patient is undergoing steroidal treatment with periodical clinical and instrumental follow-up, with poor response from the cutaneous lesions but an improvement of the pulmonary symptoms. Scalp sarcoidosis is a not frequent finding (1). Most of the reported cases are Afro-American female patients. Although the main clinico-pathological differential diagnosis is atypical necrobiosis lipoidica, this entity differs from cutaneous sarcoidosis by an absence of scalp scarring alopecia and by the fact that the annular lesions are often limited to the face, without involving the scalp (1-4). Additionally, histologically atypical necrobiosis lipoidica does not reach the typical features of a sarcoid granuloma. Other potential misdiagnoses are morphea, discoid lupus erythematosus, and lichen plano-pilaris (1-4). Sarcoidosis is most likely driven by a putative antigen in genetically susceptible individuals (5). Although radiation exposure is one of the possible causes of sarcoidosis, the radiotherapy used for the fungal infection did not have any role in the onset of the disease in our patient, as confirmed by the normal total regrowth of the hairs and the long-time interval. Regarding the therapy (mainly steroids, azathioprine, and hydroxychloroquine), if compared to other anatomical sites, the grade of atrophy in the scalp is always too high to allow an objective clinical response, as observed in our patient. This case emphasizes that in cutaneous annular sarcoidosis of the scalp, an underlying systemic sarcoidosis is often present.
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December 2017

Bullous pemphigoid with hyperkeratosis and palmoplantar keratoderma: Three cases.

J Dermatol 2018 Sep 14;45(9):1135-1140. Epub 2018 Jul 14.

Istituto Dermopatico dell'Immacolata-IRCCS, FLMM, Rome, Italy.

The clinical features of bullous pemphigoid are extremely polymorphous. Several atypical forms of bullous pemphigoid have been described, and the diagnosis critically relies on immunopathological findings. We describe three bullous pemphigoid patients characterized by palmoplantar keratoderma, diffused hyperkeratotic cutaneous lesions and extremely high levels of immunoglobulin E serum. The diagnosis of bullous pemphigoid should be taken into account in patients presenting diffused hyperkeratotic cutaneous lesions and palmoplantar keratoderma, even in the absence of blisters. Alteration of the keratinization process, that could occur in patients with genetic mutations in desmosomal and hemidesmosomal genes, may also be due to circulating autoantibodies against hemidesmosomal proteins in these bullous pemphigoid patients.
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http://dx.doi.org/10.1111/1346-8138.14529DOI Listing
September 2018