Safe distance, safe patients! Therapeutic management of oncological patients affected by cutaneous and mucosal adverse events during the COVID-19 pandemic: an Italian experience.

Stringent measures have been taken to contain COVID-19 spread, limiting access only for urgent visits, surgery procedures, or hospitalizations and using teledermatology services for non-urgent cases. Management of oncological patients affected by chemo-, immune-, and radiotherapy-related cutaneous and mucosal adverse events is a challenge. Firstly because of the differential diagnosis of cutaneous rash (e.g., drug-related rash or paraviral exanthema). Secondly, oncological patients can suffer from xerosis, pruritus, and mucositis that contribute to cutaneous and mucosal barrier lesions, thus becoming vulnerable site for viral or bacterial colonization. These lesions can also be aggravated by the use of protective mask and gloves. Here, we report also our results of a teledermatological survey on 87 oncological patients, where the health status of oncological patients referred to our dedicated clinic was assessed during the COVID-19 pandemic. Therefore, it is fundamental that oncological patients are followed up by their dermatologists even if the clinics are closed. Teledermatology represents a crucial means of communication. Patients can contact the dermatological staff by emails and telephone, 24 h a day, 7 days a week, for video calls and dermatological consultations.

Treatment of human polyomavirus-7-associated rash and pruritus with topical cidofovir in a lung transplant patient: Case report and literature review.

Human polyomavirus-7-associated rash and pruritus (PVARP) is a chronic superficial viral skin infection, which primarily impacts immunocompromised individuals. We report on a case of PVARP in a lung transplant recipient. Our patient developed symptoms 13 years after being on his immunosuppressive regimen, with an insidious course of progressive gray lichenification with marked islands of sparing and quality of life-altering pruritus. Treatment for PVARP is not established; however, topical cidofovir combined with immunomodulation may offer sustained therapeutic benefit.

Adult-onset papular purpuric gloves and socks syndrome.

Papular purpuric gloves and socks syndrome (PPGSS) is a self-limited exanthem that presents as painful or pruritic edema, erythema, petechiae, and purpura of the palms and soles with occasional extension to the dorsal hands and feet. The majority of PPGSS cases reported in the literature are associated with parvovirus B19 and occur in children and young adults. In a recent literature search, there were 11 PPGSS cases in adults with none reporting Epstein-Barr virus (EBV) as a viral etiology. However, there have been PPGSS cases related to EBV in children. We report the case of a 72-year-old man with PPGSS associated with Epstein-Barr virus. This case report serves as a reminder that PPGSS can present not only in the setting of pediatric and young adult parvovirus B19 infection, but also in immunocompetent adults with other viral infections.

Human polyomavirus 6 and 7 are associated with pruritic and dyskeratotic dermatoses.

BACKGROUND: Human polyomavirus (HPyV)6 and HPyV7 are shed chronically from human skin. HPyV7, but not HPyV6, has been linked to a pruritic skin eruption of immunosuppression. OBJECTIVE: We determined whether biopsy specimens showing a characteristic pattern of dyskeratosis and parakeratosis might be associated with polyomavirus infection. METHODS: We screened biopsy specimens showing "peacock plumage" histology by polymerase chain reaction for HPyVs. Cases positive for HPyV6 or HPyV7 were then analyzed by immunohistochemistry, electron microscopy, immunofluorescence, quantitative polymerase chain reaction, and complete sequencing, including unbiased, next-generation sequencing. RESULTS: We identified 3 additional cases of HPyV6 or HPyV7 skin infections. Expression of T antigen and viral capsid was abundant in lesional skin. Dual immunofluorescence staining experiments confirmed that HPyV7 primarily infects keratinocytes. High viral loads in lesional skin compared with normal-appearing skin and the identification of intact virions by both electron microscopy and next-generation sequencing support a role for active viral infections in these skin diseases. LIMITATION: This was a small case series of archived materials. CONCLUSION: We have found that HPyV6 and HPyV7 are associated with rare, pruritic skin eruptions with a distinctive histologic pattern and describe this entity as "HPyV6- and HPyV7-associated pruritic and dyskeratotic dermatoses."

Leflunomide for the treatment of trichodysplasia spinulosa in a liver transplant recipient.

Trichodysplasia spinulosa (TS) is a rare dermatologic complication associated with the immunosuppressive therapy used in solid organ transplantation. The distinctive clinical manifestation of this condition is spiny follicular papules on the face, ears, extremities, and trunk. Histopathologically, abnormally maturing hair follicles with hyperkeratotic material are noted. The condition is produced by the trichodysplasia spinulosa-associated polyomavirus. Treatment of this condition in the past has entailed a reduction in immunosuppression, topical agents such as cidofovir or retinoids, or oral valganciclovir. Herein, we report a case of generalized TS treated successfully with leflunomide.

In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy.

Amitriptyline/Ketamine as therapy for neuropathic pruritus and pain secondary to herpes zoster.

Frequent causes of morbidity secondary to herpes zoster include acute pain, secondary infection, and postherpetic neuralgia. A less documented complication is pruritus, which can be either acute or postinfectious when it persists more than 3 months after the rash has healed. We discuss a case of severe, acute neuropathic pruritus and pain secondary to active herpes zoster that was unresponsive to standard medical therapy, including oral antihistamines, topical lidocaine, oral gabapentin, and local wound care. Modest control of the pruritus and pain was achieved with continued multimodal therapy and the addition of topical 2% amitriptyline/0.5% ketamine gel.

Pruritic papular eruption and eosinophilic folliculitis associated with human immunodeficiency virus (HIV) infection: a histopathological and immunohistochemical comparative study.

BACKGROUND: Among the papular-pruriginous dermatoses related to human immunodeficiency (HIV) infection, two entities remain poorly differentiated leading to confusion in their diagnosis: HIV-related pruritic papular eruption (HIV-PPE or prurigo) and eosinophilic folliculitis (HIV-EF). OBJECTIVE: To establish histopathological and immunohistochemical parameters to differentiate between two conditions associated with HIV infection, the pruritic papular eruption (HIV-PPE) and eosinophilic folliculitis (HIV-EF). METHODS: Clinically typical HIV-PPE (18 cases) and HIV-EF (10 cases) cases were compared with each other in terms of the following topics: clinical and laboratory features (gender, age, CD4+ cell and eosinophil count), histopathological features (hematoxylin-eosin and toluidine blue staining) and immunohistochemical features (anti-CD1a, anti-CD4, anti-CD7, anti-CD8, anti-CD15, anti-CD20, anti-CD30, anti-CD68/macrophage and anti-S-100 reactions). RESULTS: Among the HIV-EF patients, we found an intense perivascular and diffuse inflammatory infiltration compared with those patients with HIV-PPE. The tissue mast cell count by toluidine staining was higher in the HIV-EF patients, who also presented higher expression levels of CD15 (for eosinophils), CD4 (T helper), and CD7 (pan-T lymphocytes) than the HIV-PPE patients. LIMITATIONS: Only quantitative differences and not qualitative differences were found. CONCLUSIONS: These data indicate that HIV-related PPE and EF could possibly be differentiated by histopathological and immunohistochemical findings in addition to clinical characteristics. In fact, these two inflammatory manifestations could be within the spectrum of the same disease because only quantitative, and not qualitative, differences were found.

Beyond zoster: sensory and immune changes in zoster-affected dermatomes: a review*.

Neuroepidermal tropism of varicella-zoster virus accounts for cutaneous and nerve lesions following herpes zoster. Skin lesions heal in a few weeks and may or may not leave visible scars. Nerve lesions involve peripheral sensory fibres, sometimes causing permanent damage that results in partial denervation of the affected dermatome. The effects of the nerve injury involve the sensibility function, thus causing neuralgia, itch, allodynia, hypo- or anaesthesia, as well as the immune function that is related to neuropeptide release, thus altering immune control in the affected dermatome. The neuro-immune destabilization in the zoster-infected site paves the way for the onset of many and various immunity-related disorders along the affected dermatome.

Immunohistochemical detection of parvovirus B19 in "gloves and socks" papular purpuric syndrome: direct evidence for viral endothelial involvement. Report of three cases and review of the literature.

Papular-purpuric "gloves and socks" syndrome is a distinctive dermatosis featuring acral pruritus, edema, and petechiae. It has been attributed in most--but not all--reported cases to Parvovirus B19 infection, on the grounds of serological proof of recent infection or detection of viral DNA by polymerase chain reaction in patient serum or biopsies. We report the immunohistochemical detection of Parvovirus B19 VP2 structural protein in the endothelial lining of dermal blood vessels in 3 examples of Papular-purpuric "gloves and socks" syndrome and review previously described immunohistochemical investigations in cutaneous involvement by this infection.

Association of Allergic Symptoms with Dengue Infection and Severity: A Systematic Review and Meta-analysis.

The relationship between the severity of dengue infection and allergy is still obscure. We conducted an electronic search across 12 databases for relevant articles reporting allergic symptoms, dengue infection, and dengue classification. These studies were categorized according to dengue severity and allergy symptoms, and a meta-analysis was performed by pooling the studies in each category. Among the included 57 articles, pruritus was the most common allergic sign followed by non-specified allergy and asthma (28.6%, 13%, and 6.5%, respectively). Despite the reported significant association of dengue with pruritus and total IgE level (P < 0.05), in comparison with non-dengue cases and healthy controls, there was no association between the different severe dengue group with pruritus, skin allergy, food allergy or asthma. However, removing the largest study revealed a significant association between asthma with dengue hemorrhagic fever (DHF) rather than dengue fever (DF). In comparison with DF, DHF was associated with IgE positivity. Furthermore, specific-IgE level was higher in secondary DF rather than primary DF. There was a possible association between allergy symptoms and dengue severity progression. Further studies are needed to clarify this association.

[Ocular complications in eruptive diseases of childhood]. / Complicatii oculare în bolile eruptive ale copilariei.

Childhood infectious diseases are not usually serious. The symptoms (fever, conjunctivitis, itching) diminish with the administration of antipyretic drugs. Cutaneous lesions leave no scarring. Sometimes complications may appear.

Lichen planus and other cutaneous manifestations in chronic hepatitis C: pre- and post-interferon-based treatment prevalence vary in a cohort of patients from low hepatitis C virus endemic area.

BACKGROUND: Several controversies exist regarding the relationship between hepatitis C virus (HCV) infection and some cutaneous manifestations, lichen planus (LP) in particular. OBJECTIVES: To determine the prevalence of LP and other cutaneous manifestations in a cohort of patients infected with HCV from low HCV endemic area of Slovenia, to correlate findings with chosen biological variables and to assess the role of interferon (IFN)-based treatment of HCV infection in cutaneous manifestations. Methods A total of 171 consecutive HCV-seropositive patients and 171 HCV-seronegative age- and gender-matched controls were studied prospectively. Prevalence of cutaneous manifestations, comparison between study patients and controls and correlation of skin findings with demographic, biochemical, virological and liver histologic findings as well as IFN-based therapy were assessed. RESULTS: Overall presence of LP in HCV-seropositives was 2.3%; although LP was not found in controls, the difference was not statistically significant (P = 0.123). Significantly higher than in controls was the prevalence of pruritus (31.0%, P < 0.001), dry skin (16.4%, P < 0.001) and hair loss (9.9%, P < 0.001). In IFN-based treatment naïves, skin findings were more frequent compared with controls, but not significantly, with no correlation to chosen biological variables. Current IFN-based treatment was significantly connected to pruritus (P < 0.001) and dry skin (P < 0.001). Compared with treatment naïves, in post-treated patients pruritus (odds ratio, 19.13; 95% confidence interval, 6.85-53.42; P < 0.001), dry skin (odds ratio, 4.21; 95% confidence interval, 1.44-12.31; P < 0.001) and hair loss (P < 0.001) were significantly more common. CONCLUSIONS: LP was not significantly related to HCV infection. Prevalence of pruritus, dry skin and hair loss was significantly higher in post-compared with pre-treated patients. The role of IFN in post-treatment persistence of skin manifestations needs to be assessed.

Is acyclovir effective for the treatment of varicella in children and adolescents? / ¿Es efectivo el aciclovir en el tratamiento de la varicela en niños y adolescentes?

INTRODUCTION: Varicella (chickenpox) is a frequent and highly contagious infectious disease, caused by the Varicella zoster virus. Traditionally, it has been recommended to focus on the management of symptoms, since there is controversy about the role of antivirals, particularly in children and adolescents. METHODS: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified three systematic reviews including three studies overall, all of them corresponding to randomized trials. We concluded the use of acyclovir might not decrease the associated complications, and it is not clear whether it reduces lesions or itching because the certainty of the evidence is very low.

INTRODUCCIÓN: La varicela es una enfermedad infecciosa frecuente y altamente contagiosa, producida por el virus Varicella Zoster. Tradicionalmente se ha recomendado tratarla en forma sintomática, ya que existe controversia en relación a la utilidad del tratamiento antiviral, en especial en niños y adolescentes. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos tres revisiones sistemáticas, que en conjunto incluyen tres estudios primarios, todos correspondientes a ensayos aleatorizados. Concluimos que el uso de aciclovir podría no disminuir las complicaciones asociadas, y no está claro si disminuye las lesiones o el prurito porque la certeza de la evidencia es muy baja.