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Background: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations, but SARS-CoV-2 RNA in lesional skin has been demonstrated only in few cases. Objective: To demonstrate SARS-CoV-2 presence in skin samples from patients with different COVID-19-related cutaneous phenotypes. Methods: Demographic and clinical data from 52 patients with COVID-19-associated cutaneous manifestations were collected. Immunohistochemistry and digital PCR (dPCR) were performed in all skin samples. RNA in situ hybridization (ISH) was used to confirm the presence of SARS-CoV-2 RNA. Results: Twenty out of 52 (38%) patients presented SARS-CoV-2 positivity in the skin. Among these, 10/52 (19%) patients tested positive for spike protein on immunohistochemistry, five of whom had also positive testing on dPCR. Of the latter, one tested positive both for ISH and ACE-2 on immunohistochemistry while another one tested positive for nucleocapsid protein. Twelve patients showed positivity only for nucleocapsid protein on immunohistochemistry. Conclusions: SARS-CoV-2 was detected only in 38% of patients, without any association with a specific cutaneous phenotype, suggesting that the pathophysiology of cutaneous lesions mostly depends on the activation of the immune system. The combination of spike and nucleocapsid immunohistochemistry has higher diagnostic yield than dPCR. Skin persistence of SARS-CoV-2 may depend on timing of skin lesions, viral load and immune response.

Background: Since the beginning of the coronavirus disease 2019 (COVID-19) pandemic, an increasing number of chilblain-like lesions (ChLL) have been increasingly reported worldwide. To date, the causal link between ChLL and SARS-CoV-2 infection has not been unequivocally established. Methods: In this case series, we present demographic, clinical, laboratory, and histopathological information regarding 27 young patients with a clinical diagnosis of ChLL who referred to the Dermatology Unit of Papa Giovanni XXIII Hospital, Bergamo, Italy, from 1 April 2020 to 1 June 2020. Results: The mean age was 14.2 years, and 21 patients (78%) experienced mild systemic symptoms a median of 28 days before the onset of cutaneous lesions. ChLL mostly involved the feet (20 patients – 74%). Among acral lesions, we identified three different clinical patterns: (i) chilblains in 20 patients (74%); (ii) fixed erythematous macules in 4 children (15%); (iii) erythrocyanosis in 3 female patients (11%). Blood examinations and viral serologies, including parvovirus B19, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and coxsackievirus were normal in all. Three patients (11%) underwent nasopharyngeal swab for RT-PCR for SARS-CoV-2 showing only 1 positive. Histopathological examinations of 7 skin biopsies confirmed the clinical diagnosis of chilblains; vessel thrombi were observed only in 1 case. Our findings failed to demonstrate the direct presence of SARS-CoV-2 RNA in skin biopsies, both with real-time polymerase chain reaction (RT-PCR) and RNAscope in situ hybridization (ISH). Limitations: Limited number of cases, unavailability of laboratory confirmation of COVID-19 in all patients, potential methodological weakness, and latency of skin biopsies in comparison to cutaneous lesions onset. Conclusions: These observations may support the hypothesis of an inflammatory pathogenesis rather than the presence of peripheral viral particles. Although, we could not exclude an early phase of viral endothelial damage followed by an IFN-I or complement-mediated inflammatory phase. Further observations on a large number of patients are needed to confirm this hypothesis.

Introduction: pemphigus vulgaris is a rare autoimmune blistering disease that involves the skin and mucous membranes and rarely occurs in pediatric age. Methods: we present a case of childhood pemphigus in a 9-year-old patient from Burkina Faso, which initially manifested with erosive lesions symmetrically distributed in the oral cavity. After a few months, we also observed hyperchromic lesions of the back. Histopathological examination of skin samples showed intraepidermal acantholysis, while direct immunofluorescence showed deposits of complement (C3) and immunoglobulins G (IgG) in the epidermidis; an ELISA test highlighted the presence of circulating autoantibodies against desmoglein 3. Results: the follow-up of this patient was made difficult by the advent of the COVID-19 outbreak. However, after about one year of combined therapy with systemic steroids and azathioprine the patient reached clinical remission.

Background COVID-19 is associated with a wide range of skin manifestations. Objective To describe the clinical characteristics of COVID-19-associated skin manifestations, and explore the relationships between the six main cutaneous phenotypes and systemic findings. Methods Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical and histopathological data of 200 patients with COVID-19-associated skin manifestations. The severity of COVID-19 was classified as asymptomatic, mild, moderate, or severe. Results A chilblain-like acral pattern significantly associated with a younger age (p, There are six main COVID-19-related cutaneous phenotypes, but only the chilblain-like acral pattern significantly associated with younger age. After adjusting for patient age, there was no spectrum of COVID-19 severity in relation to cutaneous phenotypes, although the longer-lasting chilblain-like acral pattern significantly associated with milder disease.

Atopic dermatitis (AD) is a chronic inflammatory skin disease. Patients with AD have increased infection risk, including skin infections and systemic infections. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for interleukin‐4 (IL‐4) and IL‐13. Dupilumab is approved for inadequately controlled moderate‐to‐severe AD.1

The antimalarials, Chloroquine and Hydroxychloroquine (HCQ), and the antivirals Lopinavir/Ritonavir have been recently recorded as having anti‐severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) effects.1 In particular, regarding Italy, one of the countries most affected by the pandemic, the Italian Society of Infectious and Tropical disease (Lombardy section) has recommended the use of HCQ for treatment of coronavirus disease 2019 (COVID‐19).

Bullous pemphigoid (BP) and pemphigus vulgaris (PV) are blistering disorders associated with barrier disruption, immune dysregulation and use of immunosuppressing systemic therapy. Patients with BP and PV have higher potential risk factors for infections secondary to skin alterations, comorbidity and chronic treatment with immunosuppressing agents.

Since the beginning of the pandemic of Coronavirus disease (COVID‐19) an increasing number of skin manifestations have been reported.1,2 Most reports concern adult patients and describe various patterns of skin eruptions, in most of cases with low specificity and no univocal temporal association with the onset of systemic symptoms of COVID‐19.1‐3

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy derived from precursors of plasmacytoid dendritic cells. We analyzed 21 cases with array-based comparative genomic hybridization (aCGH). Complete or partial chromosomal losses largely outnumbered the gains, with common deleted regions involving 9p21.3 (CDKN2A/CDKN2B), 13q13.1-q14.3 (RB1), 12p13.2-p13.1 (CDKN1B), 13q11-q12 (LATS2), and 7p12.2 (IKZF1) regions. CDKN2A/CDKN2B deletion was confirmed by FISH. This scenario argues for disruption of cell cycle at G1/S transition, representing a genetic landmark of BPDCN, and possibly contributing to its pathogenesis. Statistical analysis of overall survival in our series highlighted an association of poor outcome with biallelic loss of locus 9p21.3. We suggest that, in the absence of reliable parameters for predicting prognosis in BPDCN other than age, tumor stage, and/or clinical presentation, simple methods, such as FISH for CDKN2A/CDKN2B, could help to identify the most aggressive cases.

Background: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) primarily presenting on the skin is an extremely rare entity with only sporadic cases reported in the literature. Methods: We here report an extraordinary case of primary cutaneous THRLBCL with self-healing and 24 months of follow-up. Results: The lesion was a dermohypodermal/subcutaneous circumscribed ulcerated nodosity. Histological examination with immunohistochemical, molecular analysis and comparative genomic hybridization were performed. A complete staging was negative for secondary involvement. Conclusion: Our case is remarkable because it is the second well-documented primary cutaneous THRLBCL in which we observed a complete self-regression of skin lesions without recurrences or dissemination of the disease. According to the literature, we highlight that the tumoral microenvironment, in our case, could play a relevant role in stopping lymphoma growth. Furthermore, this case supports the observation that THRLBCL primarily presenting on the skin shows an overall good prognosis.

Regulatory T (Treg) cells, which represent 5% to 10% of peripheral T cells, regulate the activities of T-cell subsets by performing immunosuppressive functions and thus preventing the development of autoimmune responses. The majority of Treg cells are CD4 + , CD25 + , and FOXP3 + . Recently, it has been demonstrated that the tumor cells in adult T-cell leukemia lymphomas can function as Treg, raising the question of whether any variant of primary cutaneous T-cell lymphoma may also express a regulatory phenotype. We describe an extraordinary case of primary cutaneous T-cell lymphoma clinically characterized by protean cutaneous manifestations and histologically showing a pattern consistent with epidermotropic pleomorphic medium-/large-cell primary cutaneous T-cell lymphoma. The majority of neoplastic cells were CD4 + CD25 + T cells and strongly expressed FOXP3. With this background, the current case, characterized by an aggressive course requiring polychemotherapy, may support the existence of lymphoproliferative malignancies of Treg cells.

Paraneoplastic pemphigus (PNP) is a life-threatening, autoimmune, blistering-skin disease, associated with various neoplasms, particularly lymphoproliferative disorders. It is characterized by polymorphic cutaneous manifestations, severe mucosal erosions and internal organ involvement, and marked by unique histopathological features and a complex autoantigenic profile. To define this condition, the encompassing term 'paraneoplastic autoimmune multiorgan syndrome' has also been suggested. Although a number of immunosuppressive treatments have been used in PNP, its mortality rate remains high. The anti-CD20 monoclonal antibody, rituximab, was successfully administered to two patients with PNP and CD20(+) follicular lymphoma in 2001. Since then, good responses to rituximab by different refractory autoimmune disorders have been reported, but further controlled trials are warranted to evaluate the effectiveness and safety of this agent as a second-line treatment for PNP.

We describe the case of a 17-year-old Hispanic boy who had had erythroderma and diffuse lymphadenopathy for approximately 6 months. A diagnosis of Sezary syndrome was made on the basis of the histologic features of the skin; the presence of the same T-cell clone on the skin, blood, and bone marrow; and the high CD4(+) lymphocyte count with an aberrant phenotype in peripheral blood; bone marrow involvement was also present. The patient was treated with systemic gemcitabine and achieved partial remission.

Lymphoblastic lymphoma (LBL) is a neoplasm of precursor B- or T-lymphocytes, and primary skin involvement is uncommon. The aim of the study was to review all reported primary cutaneous (PC)-LBLs and to examine three new cases to better characterize this neoplasm. Two of our patients showed a pre-B phenotype (PC-B-LBL) and one a never-reported pre-T phenotype (PC-T-LBL). The patient with PC-T-LBL showed an aggressive course, while those with PC-B-LBL showed a complete remission (CR) after polychemotherapy. Cytogenetic analysis and gene expression profiling (GEP) were performed on one case of PC-B-LBL and on that of PC-T-LBL. A specimen of PC-B-LBL and two specimens (early and late stage) of PC-T-LBL were investigated by microarray-based comparative genomic hybridization (CGH). All specimens revealed trisomy of chromosome 4. PC-T-LBL showed a gain of 1p36.33-p22.1 in the early stage and multiple chromosome gains/losses in the late stage. Our data suggest that trisomy 4 could be detected early in LBL and gain of 1p36.33-p22.1 could be an interesting marker in PC-T-LBL. LBL is an aggressive disease but, only in B-LBL, the cutaneous presentation seems to be a favorable prognostic factor and polychemotherapy is the best therapeutic approach. We suggest that PC-LBL should be included as a provisional clinicopathologic entity in future cutaneous lymphoma classification. © 2012 Informa UK, Ltd.

Extranodal natural killer/T-cell (ENK/T) lymphoma is a rare neoplasm, subcategorized into ENK/T-nasal (ENK/T-N) and ENK/T-nasal type (ENK/T-NT) lymphomas. ENK/T-NT lymphoma with initial presentation in the skin is known as primary cutaneous ENK/T-NT (PC-ENK/T-NT) lymphoma. The aim of this study was to investigate pathogenesis, genomic alterations, and prognosis of cutaneous ENK/T lymphomas to provide further insights into clinicopathologic features and genetic mechanism of lymphomagenesis. A retrospective case study of 5 white patients affected by ENK/T lymphoma (4 PC-ENK/T-NT and 1 ENK/T-N with cutaneous involvement) was performed. Most of the cases presented with multiple nodules and ulcerations localized on the extremities. A considerable percentage had disease in advanced stage with a 12-month survival rate of 40%. Genomic alterations were detected by array-based comparative genomic hybridization that showed gains of 1q, 7q and loss of 17p in the cases of PC-ENK/T-NT lymphomas and gain of 7q and loss of 9p, 12p, 12q in the case of ENK/T-N lymphoma. In conclusion, ENK/T lymphoma is a very aggressive entity, and, in our cases, the exclusively cutaneous presentation was not associated with a better prognosis. The results of our array comparative genomic hybridization analysis could be useful to better define the different ENK/T lymphoma subgroups with cutaneous involvement.

Drug-induced lupus erythematosus (DILE) is defined as an entity characterized by clinical manifestations and immunopathological serum findings similar to those of idiopathic lupus but which is temporally related to continuous drug exposure and resolves after discontinuation of the offending drug. Similar to idiopathic lupus, DILE can be divided into systemic lupus erythematosus (SLE), subacute cutaneous lupus erythematosus (SCLE) and chronic cutaneous lupus erythematosus (CCLE). Based on the literature review and retrospective analysis of our case series, we focused on the dermatological aspects of DILE. The cutaneous features of drug-induced SLE are protean, including particularly purpura, erythema nodosum and photosensitivity as well as the skin lesions characterizing both urticarial and necrotizing vasculitis. The typical laboratory profile of systemic DILE consists of positive antinuclear antibodies (ANA) and antihistone antibodies, the latter being regarded as the serum marker of this subset. The drugs most frequently implicated in the development of systemic DILE are hydralazine, procainamide, isoniazid and minocycline. Drug-induced SCLE usually presents with annular polycyclic or papulosquamous cutaneous manifestations as in the idiopathic form, but blisters or targetoid lesions mimicking erythema multiforme cannot rarely be associated. The clinical presentation is often generalized, with involvement of the lower legs that are usually spared in idiopathic SCLE. ANA and anti-Ro/SSA antibodies are usually present, whereas antihistone antibodies are uncommonly found. Drugs associated with SCLE include particularly calcium channel blockers, angiotensin-converting enzyme inhibitors, thiazide diuretics, terbinafine and the recently reported tumour necrosis factor (TNF)-α antagonists. Drug-induced CCLE is very rarely described in the literature and usually refers to fluorouracile agents or TNF-α antagonists. The picture is characterized by the occurrence of classic discoid lesions, but aspects of lupus tumidus can occasionally develop. ANA are demonstrated in around two-thirds of the cases. Management of DILE is based on the withdrawal of the offending drug. Topical and/or systemic corticosteroids and other immunosuppressive agents should be reserved for resistant cases.

Auteur(s) : Amilcare Cerri1, Pamela Vezzoli2, Stefano M Serini2, Carlo Crosti2, Emilio Berti3, Angelo V Marzano2 1Dipartimento di Medicina, Chirurgia e Odontoiatria, Polo San Paolo, Universita degli Studi di Milano, Milan, Italy 2U.O. Dermatologia, Fondazione IRCCS Ca’ Granda - Ospedale Maggiore Policlinico Dipartimento di Anestesiologia, Terapia Intensiva e Scienze Dermatologiche, Universita degli Studi di Milano, Via Pace 9- 20122 Milan, Italy 3Universita degli Studi di Milano-Bicocca Mycosis [...]

Background Wells syndrome, an uncommon inflammatory dermatosis, is characterized by protean cutaneous manifestations, suggestive but not specific histopathologic findings, and usually a recurrent course. Because of its original description as a distinct entity, it has come to be regarded as an abnormal eosinophilic response to a number of causative agents. Observations The medical records of 19 patients (12 adults and 7 children) with Wells syndrome referred to the Institute of Dermatological Sciences from 1990 to 2005 were evaluated for the type and prevalence of skin lesions, clinical course and response to treatment, and possibly associated systemic symptoms, as well as histologic, laboratory, and immunofluorescence findings. The classic plaque-type variant proved to be the most common presentation in children but not in adults, who more frequently had the annular granuloma–like variant. Unilesional forms were found to occur more frequently in children. The course was recurrent, although slowly progressing, with a mean duration of disease of 5 years for adults and 3 years for children. Conclusions We emphasize the concept that the diagnosis of Wells syndrome is a clinicopathologic diagnosis. Although it should be classified within a spectrum that includes multisystem eosinophilic disorders, such as Churg-Strauss and hypereosinophilic syndromes, Wells syndrome, which has 7 variants, is a distinct cutaneous disease lacking systemic involvement.

We describe a male patient with rosacea who had a 2-year history of persistent bilateral oedema of the eyelids, leading to an elephantoid condition with blepharoptosis. An upper eyelid blepharoplasty was performed, but swelling progressively recurred over a few months. Based on the case history, clinical appearance and histological findings, rosaceous lymphoedema was considered to be the diagnosis. The latter is a bilateral, solid oedema of the mid-third of the face, regarded as a rare complication of rosacea. It is thought to occur as a result of chronic inflammation and lymphatic stasis, but its exact aethiopathogenesis remains elusive. Predominant eyelid involvement, causing severe visual impairment as in our patient, is unique.

Cutaneous leishmaniasis (CL) is an infection caused by protozoa from the genus Leishmania. The disease is transmitted by sandflies. Reservoirs are dogs, mice, wild rodents and, more rarely, humans. CL is clinically characterized by a single, polymorphous lesion, usually localized on the face or limbs. Nowadays, CL is more frequently seen among travellers returning from tropical and subtropical countries (1). Cutaneous lymphoid hyperplasia (CLH), also known as pseudolymphoma, is a reactive proliferation, probably secondary to persistent antigenic stimulation. We present here a case of CLH associated with L. panamensis infection.

Abstract 3565 Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, haematologic malignancy. The disease may occur at any age, with strong male predominance. Skin presentation is very common. Histologically, tumour cells constitute a uniform population of round or more pleomorphic medium size elements. Clinically this tumour is very aggressive, with poor outcome in adults (median survival 13 months). Chemotherapy (CT), preferably with acute leukemia-type regimens, is the mainstay of treatment, when possible associated with stem cell transplantation (SCT). Few studies investigated copy number changes by array-based comparative genomic hybridization (array-CGH) and gene expression profiling, highlighting a peculiar set of chromosomal losses involving regulatory genes. The present study focused on 23 cases of BPDCN, that were extensively investigated cytogenetically (array-CGH and SNP6 array) and immunohistochemically. Clinico-pathologic findings and molecular data were analyzed in order to identify prognostic markers and possible clinical subsets. At onset 12 cases had diffuse, 7 multiple non contiguous and 4 localized skin involvement. Cases 16 and 18 were father and his daughter. Specific therapy was administered in 20 cases: 10 ALL-type CT; 4 NHL-type CT; 2 mono-CT with 1 radiotherapy; 2 radiotherapy alone; 2 SCT. Ten patients relapsed, in a median time of 10 months: 9 cases received further CT and 2 underwent allo-SCT. At last follow-up, 11 patients had died of disease and 2 of therapy-related causes. Median overall survival (OS) was 21 months. At last follow-up 10 patients were alive, 6 disease-free (8 to 28 months) and 4 with disease. Immunophenotype was typical (CD4, CD56, BDCA2, Tcl-1, and CD123) in all but three patients: 1 negative both for CD4 and CD56, 1 for CD56 and 1 for CD4. All cases expressed CD45RA, 19 CD68/KP1, 10 CD2 and/or CD7 and, when tested, for BDCA2/CD303. T-cell and B-cell receptor genes were germline with no evidence of EBV infection. We observed chromosomal imbalances in all patients. Loss of CDKN2A locus (9p21.3) occurred in 15/23 patients, and in 5 cases a biallelic loss was found. FISH confirmed 9p21.3 loss in all 5 cases. Of note, patients with biallelic loss of locus 9p21.3, in respect to those with hemizygous loss, had reduced survival probability (hazard ratio 11.98; confidence interval [CI] 1.21–118.96; log-rank test, p=0.0349). Median OS was 20 and 35 months and median time to relapse 11 and 15 months, respectively. Furthermore, loss of RB1 (13q13.1-q14.3) and CDKN1B (12p13.2-p13.1) locus were observed in 13 cases. An additional, yet unreported, cytogenetic alteration was the loss of 7p12 in 5 of our patients. This is the locus of IKZF1 gene, which encodes the transcription factor Ikaros. Of note, biallelic and monoallelic deletions of IKZF1 has been shown to be associated with chemoresistance and very poor outcome in a subset of BCR-ABL1 positive acute lymphoblastic leukemias. Array-CGH and SNP6 in our series confirmed that BPDCN is characterized by a complex pattern of genomic losses, predominantly affecting chromosomes 9 (71%), 13 (61%), 12 (57%), 5 (19%), 7 (19%), 14 (14%) and 15 (14%). In conclusion, this is the largest reported series of BPDCN patients, confirming high aggressiveness of the disease. We found negative correlation between age and time to relapse (p=0.0053) and a lower rate of bone marrow involvement in the group of patients with localized skin disease (2 of whom in CR after local skin radiotherapy). Furthermore, we observed absence of CD4 and/or CD56 expression in 3/23 cases. We are the first to report reduced OS probability among patients with homozygous loss of locus 9p21.3 in comparison to those with hemizygous loss, and the possible loss of 7p12-IKZF1 gene in BPDCN. Disclosures: No relevant conflicts of interest to declare.

Sir, In the treatment of cutaneous T-cell lymphomas, radiotherapy plays a well-known role in the management of mycosis fungoides (MF) and Sezary syndrome, as localized radiotherapy or total skin electron-beam irradiation. Furthermore, radiotherapy has been indicated as first choice treatment in large cell CD30+ lymphomas (LCCD30+L) (1, 2), and in pleomorphic small/medium-sized cells lymphomas (PSMSL) (1, 3, 4). The former is characterized by a single nodularulcerative lesion or grouped nodules, rarely multifocal, sometimes spontaneously regressing, showing histopathologically a diffuse non-epidermotropic infiltrate of large cells expressing CD30 phenotype. The latter is defined by the occurrence of one or several dark red nodules, due to a neoplastic infiltrate of pleomorphic small/medium-sized cells, without clinical evidence of concurrent patches typical for mycosis fungoides. In this short report we update our data on the radiological treatment of LCCD30+L (5), evaluate the results of radiotherapy in the treatment of PSMSL, and compare our findings with those reported in the literature (1–4, 6).