The clinical spectrum of COVID-19-associated cutaneous manifestations: An Italian multicenter study of 200 adult patients.

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 among the 6 main cutaneous phenotypes and systemic findings. METHODS: Twenty-one Italian Dermatology Units were asked to collect the demographic, clinical, and histopathologic 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 was significantly associated with a younger age (P < .0001) and, after adjusting for age, significantly associated with less severe COVID-19 (P = .0009). However, the median duration of chilblain-like lesions was significantly longer than that of the other cutaneous manifestations taken together (P < .0001). Patients with moderate/severe COVID-19 were more represented than those with asymptomatic/mild COVID-19 among the patients with cutaneous manifestations other than chilblain-like lesions, but only the confluent erythematous/maculo-papular/morbilliform phenotype was significantly associated with more severe COVID-19 (P = .015), and this significance disappeared after adjustment for age. LIMITATIONS: Laboratory confirmation of COVID-19 was not possible in all cases. CONCLUSIONS: After adjustment for age, there was no clear-cut spectrum of COVID-19 severity in patients with COVID-19-related skin manifestations, although chilblain-like acral lesions were more frequent in younger patients with asymptomatic/pauci-symptomatic COVID-19.

Histopathological Study of a Broad Spectrum of Skin Dermatoses in Patients Affected or Highly Suspected of Infection by COVID-19 in the Northern Part of Italy: Analysis of the Many Faces of the Viral-Induced Skin Diseases in Previous and New Reported Cases.

Skin manifestations of COVID-19 infections are diverse and are new to the dermatology community. We had the opportunity to examine the clinical and histopathological features of several patients who were divided into 3 groups. The first group included 8 COVID-19-positive patients who were hospitalized and quarantined at home. The second group included children and young adults who presented with chilblain erythema, erythema multiforme, and urticaria-like lesions. This group of patients was negative for the COVID-19 gene sequences by polymerase chain reaction but had a high risk of COVID-19 infection. The third group included clinically heterogeneous and challenging lesions. These patients were not subject to either polymerase chain reaction tests or serological analyses because they sought dermatological attention only for a dermatosis. The histopathological analysis of these cases showed a wide spectrum of histopathological patterns. What appears to be constant in all skin biopsies was the presence of prominent dilated blood vessels with a swollen endothelial layer, vessels engulfed with red blood cells, and perivascular infiltrates, consisting mainly of cytotoxic CD8+ lymphocytes and eosinophils. In 2 cases, there was diffuse coagulopathy in the cutaneous vascular plexus. In the early phases of the disease, there were numerous collections of Langerhans cells in the epidermis after being activated by the virus. The presence of urticarial lesions, chilblains, targetoid lesions (erythema multiforme-like lesions), exanthema, maculohemorrhagic rash, or chickenpox-like lesions associated with the histopathological features mentioned previously should cause clinical dermatologists to suspect the possibility of COVID-19 infection, especially in patients with fever and cough.

Anti-Herpes zoster vaccination in patients with dermatologic diseases: a position statement from the Italian SIDeMaST group of sexually transmitted, infectious and tropical diseases.

Herpes zoster (HZ) is a condition caused by the reactivation of varicella-zoster virus (VZV), the virus responsible for chickepox, which is the clinical manifestation of the primary infection. Congenital or acquired immune system deficiencies, as well as the physiological decline in immune response occurring in the elderly, known as immune senescence, can allow VZV reactivation and, consequently, HZ. One out of 3 people develops HZ during their lifetime. Moreover, thirty percent of the affected subjects develop post-herpetic neuralgia, the most frequent complication after HZ skin rash. Patients with dermatological conditions characterized by alteration of the immune system, such as systemic lupus erythematosus, psoriasis, atopic dermatitis, bullous diseases, and cutaneous lymphomas, are at higher risk of developing HZ and post-herpetic neuralgia, even when their disease is in remission. In the present work, we described the currently available vaccinations against HZ and provided recommendations for the vaccination against HZ in patients with dermatological diseases.

Intramuscular Polydeoxyribonucleotides in Fibrotic and Atrophic Localized Scleroderma: An Explorative Prospective Cohort Study.

Effective options in the quiescent, scantily inflammatory phase of localized scleroderma (morphea) are lacking. A cohort study in patients with histologically confirmed fibroatrophic morphea explored the therapeutic value of the anti-dystrophic A2A adenosine agonist polydeoxyribonucleotide (PDRN, one daily 5.625 mg/3 mL ampoule for 90 days with a three-month follow-up). Primary efficacy endpoints: Localized Scleroderma Cutaneous Assessment Tool mLoSSI and mLoSDI subscores for disease activity and damage in eighteen areas; Physicians Global Assessment for Activity (PGA-A) and Damage (PGA-D) VAS scores; skin echography. Secondary efficacy endpoints: mLoSSI, mLoSDI, PGA-A, PGA-D, and morphea areas (photographs) over time; Dermatology Life Quality Index (DLQI); skin biopsy scores and induration over time. Twenty-five patients enrolled; 20 completed the follow-up period. Highly significant improvements at the end of the 3-month treatment period: mLoSSI-73.7%, mLoSDI-43.9%, PGA-A-60.4%, PGA-D-40.3%, with further improvements at follow-up visit for all disease activity and damage indexes. Overall, the outcomes suggest that a daily PDRN ampoule intramuscularly for 90 days reduces disease activity and damage rapidly and significantly in quiescent, modestly inflammatory morphea with few currently therapeutic options. The COVID-19 pandemic and lockdowns caused difficulties in enrollment, and some patients were lost to follow-up. Due to low final enrollment, the study outcomes may have only an exploratory value, yet they appear impressive. The anti-dystrophic potential of the PDRN A2A adenosine agonist deserves further in-depth exploration.

COVID 19-associated chilblain-like acral lesions among children and adolescents: an Italian retrospective, multicenter study.

BACKGROUND: Since the COVID-19 pandemic started, great interest has been given to this disease, especially to its possible clinical presentations. Besides classical respiratory symptoms, dermatological manifestations occur quite often among infected and non-infected patients, particularly in children. A prominent IFN-I response, that is generally higher in children compared to adults, may not only cause chilblain lesions, but it could also prevent infection and viral replication, thus justifying the negative swab results, as well as the absence of relevant systemic symptoms in positive cases. Indeed, reports have emerged describing chilblain-like acral lesions in children and adolescents with either proven or suspected infection. METHODS: Patients aged from 1 to 18 years old were enrolled in this study from 23 Italian dermatological units and were observed for an overall period of 6 months. Clinical pictures were collected along with data on the location and duration of skin lesions, their association with concomitant local and systemic symptoms, presence of nail and/or mucosal involvement, as well as histological, laboratory and imaging findings. RESULTS: One hundred thirty-seven patients were included, of whom 56.9% were females. Mean age was 11.97±3.66 years. The most commonly affected sites were the feet (77 patients, 56.2%). Lesions (48.5%) featured cyanosis, chilblains, blisters, ecchymosis, bullae, erythema, edema, and papules. Concomitant skin manifestations included maculo-papular rashes (30%), unspecified rashes (25%), vesicular rashes (20%), erythema multiforme (10%), urticaria (10%) and erythema with desquamation (5%). Forty-one patients (29.9%) reported pruritus as the main symptom associated with chilblains, and 56 out of 137 patients also reported systemic symptoms such as respiratory symptoms (33.9%), fever (28%), intestinal (27%), headache (5.5%), asthenia (3.5%), and joint pain (2%). Associated comorbid conditions were observed in 9 patients presenting with skin lesions. Nasopharyngeal swabs turned out positive in 11 patients (8%), whereas the remainder were either negative (101, 73%) or unspecified (25, 18%). CONCLUSIONS: COVID-19 has been credited as the etiology of the recent increase in acro-ischemic lesions. The present study provides a description of pediatric cutaneous manifestations deemed to be potentially associated with COVID-19, revealing a possible association between acral cyanosis and nasopharyngeal swab positivity in children and teenagers. The identification and characterization of newly recognized patterns of skin involvement may aid physicians in diagnosing cases of asymptomatic or pauci-symptomatic COVID patients.

Cutaneous extranodal NK/T-cell lymphoma: a clinicopathologic study of 5 patients with array-based comparative genomic hybridization.

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.

Late-onset focal dermal elastosis: Report of a case and review of the literature.

Late-onset focal dermal elastosis is a rare cutaneous condition classified as an increased dermal elastic tissue disorder. It is distinguished clinically by multiple papules with a preference for the neck and other flexures, as well as histologically by focally increased elastic fibers in the reticular dermis. Several elastic tissue disorders in the skin have a similar clinical presentation. The distinction between late-onset focal dermal elastosis and other pseudoxanthoma elasticum mimickers is critical because they are not associated with systemic lesions. We present a case of late-onset focal dermal elastosis and conduct a literature review on this unusual condition.

Petrified Ears: A Clue for Adrenal Insufficiency.

Petrified ears is an uncommon clinical entity. It describes auricular cartilage hardening, due usually to ectopic calcification or, less commonly, ossification. The most common causes are frostbite and mechanical trauma. However, endocrinopathies have also been reported to cause ectopic calcium deposition through an unknown mechanism. Addison's disease is the systemic disease most frequently associated, but the exact pathogenesis remains unclear. Patients are usually asymptomatic, and the diagnosis is made incidentally when rigid helices are noted on palpation and can be confirmed by radiological imaging. A biopsy can also help to differentiate between calcification and ossification. The presence of this condition may be a useful clinical sign, which in some cases precedes the development of endocrinopathies by many years. We report on a case, and we review the current literature.

COVID-19: The experience from Italy.

A wide range of cutaneous signs are attributed to COVID-19 infection. This retrospective study assesses the presence and impact of dermatologic manifestations related to the spread of COVID-19 in Lombardy, the geographic district with the first outbreak in Italy. A cohort of 345 patients with laboratory confirmed COVID-19 was collected from February 1, 2020 to May 31, 2020. Cutaneous signs and dermatologic diagnoses were recorded on admission, and during the course of the disease. Of the 345 patients included in the study, 52 (15%) had new-onset dermatologic conditions related to COVID-19. We observed seven major cutaneous clinical patterns, merged under 3 main groups: Exanthems, vascular lesions, and other cutaneous manifestations. Each subset was detailed with prevalence, age, duration, prognosis, and histology. Cutaneous findings can lead to suspect COVID-19 infection and identify potentially contagious cases with indolent course.

COVID-19-related skin manifestations: Update on therapy.

An increasing body of evidence has been produced in a very limited period to improve the understanding of skin involvement in the current coronavirus 2019 disease pandemic, and how this novel disease affects the management of dermatologic patients. A little explored area is represented by the therapeutic approach adopted for the different skin manifestations associated with the infection. An overview of the current scenario is provided, through review of the English-language literature published until October 30, 2020, and comparison with the personal experience of the authors. As dermatologists, our primary aim is to support patients with the highest standard of care and relieve suffering, even with lesions not life-threatening. With asymptomatic COVID-19 patients, patient discomfort related to skin lesions should not be undervalued and intervention to accelerate healing should be provided. Consensus protocols are warranted to assess the best skin-targeted treatments in COVID-19 patients.

Cutaneous adverse effects due to personal protective measures during COVID-19 pandemic: a study of 101 patients.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) is a viral illness caused by the novel coronavirus SARS-CoV-2 which spreads via droplets from an infected person. There has been an unprecedented rise in the use of personal protective equipment and practice of personal hygiene measures against COVID-19. The extended use of protective measures (PM) can lead to ill effects on the skin. Our aim was to investigate PM-induced dermatoses amongst healthcare workers and the general population during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted over a period of 2 months. The study subjects were patients who presented to dermatology outpatient clinics or sought teleconsultation for skin problems related to the use of PMs against COVID-19. A detailed history was obtained and cutaneous examination was documented for all the patients in a pre-set proforma. Diagnoses of the adverse skin effects were formulated based upon history and clinical examination. RESULTS: A total of 101 cases with cutaneous adverse effects due to the use of PMs against COVID-19 were included in the study. The general population and healthcare workers were affected similarly, comprising of 54.5% and 45.5%, respectively. The mean age of the study participants was 36.71 ± 15.72 years. The most common culprit material was soap and water (56.4%). Contact dermatitis was found to be the most common adverse effect in the majority of our patients (72.3%). The most common symptom reported was pruritus (45.5%). The wearing of personal protective equipment for a longer duration was significantly associated with multiple symptoms (P = 0.026). CONCLUSION: The enhanced use of different PMs against COVID-19 can result in a variety of adverse skin effects. In our study, the use of soap and water was the most common culprit PM, and contact dermatitis was the most common adverse effect noted.

How Coronavirus Disease 2019 Changed Dermatology Practice in 1 Year Around the World: Perspectives from 11 Countries.

Coronavirus disease 2019 (COVID-19) brought the world to its knees. As each nation grappled with launching an effective response while simultaneously minimizing repercussions on health care systems, economies, and societies, the medical and scientific landscape shifted forever. In particular, COVID-19 has challenged and transformed the field of dermatology and the way we practice. In this article, dermatologists from 11 countries share insights gained from local experience. These global perspectives will help provide a better framework for delivering quality dermatologic care and understanding how the field has evolved during this medical crisis.

Detection of IgE autoantibodies in mucous membrane pemphigoid and their association with disease severity.

BACKGROUND: Mucous membrane pemphigoid (MMP) is an autoimmune disease characterized by scarring lesions at mucosal sites. Although the pathogenic role of specific IgG and/or IgA has been already demonstrated and the detection of these immunoglobulins is a criterion in the diagnosis of MMP, little is known about IgE role in this disease. Therefore, the main purpose of this study was to assess the presence of circulating and tissue bound IgE in patients with MMP and their possible correlations with clinical presentation and disease course. METHODS: We conducted a retrospective study on 29 patients affected by MMP, recruited from a single center. Direct and indirect immunofluorescence studies were assessed to analyze the presence of specific IgE directed against the basal membrane zone. For each patient, fluorescence data were compared to clinical features. RESULTS: Linear deposits of C3, IgG and IgA were present in 86.2%, 62% and 37.9% of cases respectively, while IgE linear deposits were detected in 17 out of 29 patients (58.6%) including one case with isolated IgE positivity. Circulating IgE and IgA anti-BMZ were present in 7 (24.1%) and 5 (17.2%) patients, respectively. Both the presence of circulating IgA and of tissue bound IgE deposits correlated with disease activity index (P<0.014). CONCLUSIONS: Our results demonstrated the presence of IgE autoantibodies in MMP, particularly in more severe cases. Thus, IgE detection may represent an additional useful diagnostic tool in this disease.