Preventing and fighting stigma: a lesson from the first Mpox in Veneto region of Northeast Italy-A case report.

Since the 1970s, human monkeypox (Mpox) has been referred to as a zoonotic endemic disease of specific regions of Africa until early 2022, when a worldwide epidemic outbreak developed. There are many hypotheses on how Mpox could spread to non-endemic regions; the dominant theory is that it spread from the UK and Spain among men who have sex with men (MSM). Therefore, the first clinical case in the Veneto region (Northeast of Italy) was analyzed-which represented a typical case report of the ongoing outbreak-with lesions located mainly in the areas associated with sexual behaviors (genital and oral). This case report highlights the new challenges of Mpox, as it seems to differ from the previous classic manifestation. Indeed, although the patient achieved restitution ad integrum of lesions and complete recovery from the disease, it is deemed necessary to offer communication strategies to involve a heterogeneous audience based on different risks of exposure but without stigmatizing attitudes, avoiding the mistakes made with HIV. The need for broad public involvement is demonstrated by identifying Mpox even in "anomalous cases." Stigma could be an obstacle in engaging patients in proper care and in getting honest answers while contact tracing, as happened in our patient's case; thus, WHO recently renamed monkeypox as Mpox. Abnormal outbreaks in non-endemic countries, with no causal links, must become a warning signal for governments and health policies to design national plans for managing unexpected outbreaks. For an effective public health response, health institutions must communicate effectively, focus on changes and prevention measures, and formulate a plan based on equity and inclusion of the most vulnerable groups.

Efficacy of a topical formulation containing MIA (Melanoma Inhibitory Activity) - Inhibitory peptides in a case of recalcitrant vitiligo in combination with UV exposure.

INTRODUCTION: Vitiligo is an acquired chronic pigmentation disorder of the skin. Even if the role of the immune system seems to be well established, new pathogenetic hypothesis are rising in these years. It has been recently suggested by the development of an animal model that a protein called Melanoma Inhibitory Activity (MIA) is involved in the pathogenesis of vitiligo. This protein interacts with the adhesion molecules expressed on the melanocytes causing its detachment from extracellular matrix proteins and creating the depigmented macules. A topical preparation based on oligopeptides able to inhibit the actions of the MIA protein has been introduced to the market, claiming activity on vitiligo. PATIENT CONCERNS AND DIAGNOSIS: A patient affected by non-segmental vitiligo for 10 years, recalcitrant to any treatment (such as steroids, immunomodulators, kellin, UVB-NB and UVA) came to our observation. INTERVENTIONS: We used this topical preparation containing the MIA inhibitors peptides in selected areas (face and sides of the trunk) leaving untreated other areas as control (legs and arms). The patient was required to be sun exposed or to have some UVA sessions during the treatment to stimulate the melanocytes replications. OUTCOMES: After 9 months of treatments, he recovered from 50% to 80% of repigmentation only in the treated areas, without any side effects locally or systemically. CONCLUSION: Even if other studies are required to better determine the efficacy of this approach, this first observation about the use of the MIA-inhibitors peptides for the treatment of non-segmental vitiligo indicates that this topical preparation containing the MIA inhibitors peptides could be a very promising option for the cure of this disease.

Melanoma Inhibitory Activity (MIA) Is Able to Induce Vitiligo-Like Depigmentation in an in vivo Mouse Model by Direct Injection in the Tail.

In the complex pathogenesis of vitiligo, the exact mechanism of the dermatosis is still to be clarified. We previously demonstrated that a protein called melanoma inhibitory activity (MIA) is present in non-segmental vitiligo skin and seems to cause the detachment of melanocytes, consequently creating the depigmented macules. In this study, we present an animal model of vitiligo on the basis of the ability of the MIA protein to induce vitiligo-like lesions. Twenty pigmented mice were chosen for the experiments and received injections in the tail with saline (control group) or with saline + MIA protein (treated group). The control group did not show any sign of depigmentation. The treated group showed, instead, clear zones of complete depigmentation in the injected areas in each mouse, with the appearance of white patches with whitening of the hair and a clear-cut edge. Histological examination of the tail in the treated zone showed the absence of melanocytes, without the presence of any inflammatory cell or any sign of skin inflammation patterns, confirming the detachment of the melanocyte operated by the MIA protein. These data seem to confirm a possible role played by the MIA protein in the pathogenesis of vitiligo and may support the development of treatments able to inhibit its action as an alternative therapeutic strategy for this disorder.

Skin cancer and other cutaneous disorders in liver transplant recipients.

Patients who have received liver transplant are at increased risk of skin complications due to long-term immunosuppression regimen. The aim of this study was to analyze the incidence and risk factors of skin complications in liver transplant patients. We analyzed 161 liver transplant recipients. The mean age at transplantation was 47.4 years. Mean follow-up was 6 years. Seventy-one percent of patients presented with skin complications, including aestethic alterations, infections, precancerous lesions and malignancies, which represented 57%, 43%, 18% and 9%, respectively. Risk factors were: age at transplantation ≥ 45 years, immunosuppressive therapy with cyclosporine, and phototype II and III. Our study indicates that although liver transplant recipients are at greater risk of developing skin complications compared to the general population, the risk is lower than for other solid organ transplants, particularly for premalignant and malignant lesions.

Adaptive immune responses in primary cutaneous sarcoidosis.

Sarcoidosis is a multisystemic inflammatory disorder with cutaneous lesions present in about one-quarter of the patients. Cutaneous lesions have been classified as specific and nonspecific, depending on the presence of nonnecrotizing epithelial cell granulomas on histologic studies. The development and progression of specific cutaneous sarcoidosis involves a complex interaction between cells of the adaptive immune systems, notably T-lymphocytes and dendritic cells. In this paper, we will discuss the role of T-cells and skin dendritic cells in the development of primary cutaneous sarcoidosis and comment on the potential antigenic stimuli that may account for the development of the immunological response. We will further explore the contributions of selected cytokines to the immunopathological process. The knowledge of the adaptive immunological mechanisms operative in cutaneous sarcoidosis may subsequently be useful for identifying prevention and treatment strategies of systemic sarcoidosis.

Bullous scabies simulating pemphigoid.

BACKGROUND: Scabies is a contagious infestation affecting subjects of all ages, races, and social conditions. OBJECTIVE: We report a case of a 79-year-old man who developed a bullous pemphigoid-like eruption. He presented to our unit 4 months after the onset of symptoms. An autoimmune bullous disease was suspected. Direct immunofluorescence on a skin specimen and anti-desmoglein 1, anti-desmoglein 3, and anti-bullous pemphigoid antigen 180 were negative. Surprisingly, the histology of a skin lesion demonstrated the presence of scabies, which was successfully treated with benzyl benzoate 20%. CONCLUSION: The diagnosis of bullous scabies should be considered for any bullous eruptions accompanied by papules and itching resistant to steroid treatment and with negative immunopathologic findings.

The role of immunohistochemical analysis in the diagnosis of parapsoriasis.

Parapsoriasis is a chronic dermatosis whose biological distinction from early mycosis fungoides, the most frequent form of cutaneous T-cell lymphoma, is still not clearly defined. Two types of parapsoriasis have been delineated: large-plaque parapsoriasis and small-plaque parapsoriasis. The lack of clinical and histological features, which may allow distinguishing parapsoriasis from early mycosis fungoides has prompted several investigations to assess the role of immunohistochemistry in establishing a conclusive diagnosis of these conditions. However, the additional data obtained by immunohistochemical analysis concerning the CD4/CD8 ratio, the aberrant expression of T-cell antigens and the expression of proliferation markers has not generally helped establish a more definitive diagnosis. This review critically discusses these immunohistochemical markers and their use in diagnosis of parapsoriasis.

Successful treatment of a 9-year-old boy affected by acrodermatitis continua of Hallopeau with targeted ultraviolet B narrow-band phototherapy.

Acrodermatitis continua of Hallopeau (ACH) consists of a relapsing pustular eruption of the distal portions of hands and feet. We described a case of a 9-year-old boy affected by ACH, successfully treated with targeted ultraviolet B 311 nm phototherapy, which seems to be an effective and safe therapy for this condition.

Immunosuppression and melanocyte proliferation.

Melanocytes are pigmented cells derived from the neural crest; their proliferation is restrained by immune system. The eruption of nevi after an immunosuppressive condition is a peculiar phenomenon indicating that the immune system may play a major role in limiting proliferation of melanocytes. In this review, we analyze the role of immunosuppressive regimens on melanocyte proliferation. In particular, we discuss the eruptive nevi phenomenon, which is determined by the inability of the immune system to inhibit melanocyte proliferation. These clinical observations indicate that the immune system has a pivotal role in restraining melanocyte proliferation. However, although the role of the immune system in the development of nonmelanoma skin cancer has been shown clearly in several studies involving organ transplant patients, the role of immunosuppression in melanoma genesis has not yet been established. Further investigations are required to establish the real immunogenicity of melanoma, particularly in the light of the dichotomy between the eruptive nevi phenomenon in immunosuppressed patients and the low incidence of melanoma in transplanted patients.

Primary cutaneous CD30+ anaplastic large cell lymphoma in a heart transplant patient: case report and literature review.

Solid organ transplant recipients are at risk of developing a wide range of viral-associated malignancies, including skin tumours and lymphoproliferative disorders. The risk of a post-transplant lymphoproliferative disorder is 28-49 times the risk of a lymphoproliferative disorder in the normal population. Most cases are of B-cell phenotype and are associated with Epstein-Barr virus infection. Post-transplant lymphoproliferative disorders presenting clinically in the skin are rare and usually of B-cell phenotype. Only rare cases of cutaneous T-cell post-transplant lymphoproliferative disorder have been reported previously, mostly mycosis fungoides type. We describe here a rare primary cutaneous T-cell lymphoma CD30+ arising in a heart transplant patient who had a nodule on the right leg, several years after heart transplantation. The morphology and immunohistochemical findings were consistent with a CD30+ anaplastic large cell lymphoma with a T-cell phenotype. Excisional biopsy and radiotherapy of the affected area were performed. In this patient, the presence of a solitary lesion and the lack of systemic involvement represented the main factors taken into account in choosing the therapy and the patient was therefore treated using a non-aggressive approach, although with systemic immunosuppression. In conclusion, the diagnosis of a CD30+ anaplastic large cell lymphoma in transplant recipients does not imply aggressive clinical behaviour by the lymphoma.

Detection of autoantibodies against recombinant desmoglein 1 and 3 molecules in patients with pemphigus vulgaris: correlation with disease extent at the time of diagnosis and during follow-up.

The recent availability of cDNA clones for pemphigus antigens has allowed the production of recombinant desmoglein 1 and desmoglein 3 molecules and the development of an ELISA approach in order to determine levels of antibodies to them. The aim of the study was to determine the relationship between autoantibodies levels and the extent of both mucosal and skin lesions in 20 patients with pemphigus vulgaris at the time of diagnosis and during follow-up. For the detection of autoantibodies by ELISA we used the recombinant proteins expressing overlapping sequences with the entire extracellular desmoglein 1 and desmoglein 3 domains. We showed that in presence of mucosal lesions there was a correlation between extension of mucosal involvement and autoantibodies titres against both desmoglein 1 and desmoglein 3, whereas in presence of skin lesions there was a statistically significant correlation between extension of skin lesions and autoantibodies titres against desmoglein 3, but not against desmoglein 1. A not negligible number of patients showed variations of the desmoglein 3 autoantibodies titre which did not correlate with the severity of both cutaneous and mucosal involvement. Similar results were obtained analyzing autoantibodies titres against desmoglein 1. In conclusion, we believe that the utilization of recombinant desmoglein 1 and desmoglein 3 proteins by ELISA should be used with caution to monitor disease severity and response to therapy, although it remains a high specific test for the initial diagnosis of pemphigus and the identification of a change in the clinical phenotype of this condition.

Primary subcutaneous B-cell lymphoma: case report and literature review.

Primary cutaneous B-cell lymphomas are defined as malignant B-cell proliferations presenting with cutaneous involvement alone and no evidence of extracutaneous manifestations when complete staging has been performed. It has been shown that the infiltrate in some cases could involve the underlying subcutaneous tissues, but primary localization in this compartment has been rarely reported. We describe here the case of a 53-year-old woman who noticed a nodular lesion on the left shoulder that rapidly enlarged in a few months. The histological and immunophenotypical features were compatible with a subcutaneous B-cell lymphoma. The tumoural mass was confined predominantly to the subcutaneous compartment, as confirmed by computed tomography. No other tumour localizations were found. Thus, primary B-cell lymphoma of the subcutis was diagnosed. We report a review of the literature indicating that B-cell lymphomas that are primarily localized to the subcutaneous tissues represent a very rare modality of presentation with a biological behaviour different from conventional cutaneous B-cell lymphoma.

γδ T cells as potential contributors to the progression of parapsoriasis to mycosis fungoides.

It has recently been demonstrated that γδ T lymphocytes play a role in innate immunity to the neoplastic process; however, the significance of this subset of T lymphocytes in the pathophysiology of the most common form of cutaneous T cell lymphomas, mycosis fungoides, has yet to be investigated. In order to identify whether γδ T lymphocytes play a role in the progression of a pre-lymphomatous stage (parapsoriasis) to frank lymphoma (mycosis fungoides), we evaluated their presence in the skin biopsies of patients affected by mycosis fungoides and parapsoriasis. The skin biopsies of ten patients with mycosis fungoides and nine patients with parapsoriasis were analyzed using immunohistochemistry with a panel of different antibodies for T cell-associated markers (CD3, CD4, CD5, CD8 and γδ TCR). The percentage of T cells expressing γδ T cell receptors (TCR) was similar in the biopsies from both groups of skin disorders, ranging from 1 to 5% of the total T cell population. We observed a constant presence of T cells bearing γδ TCR in parapsoriasis and mycosis fungoides that did not differ between the two conditions. This presence is consistent with the role played by this subgroup of T cells of the innate immunity system in the development and maintenance of the two skin disorders. However, the contribution of γδ T cells to the progression of parapsoriasis to mycosis fungoides remains to be elucidated.