RNAscope in situ hybridization and RT-PCR for detection of SARS-CoV-2 in chilblain-like lesions: A clinical, laboratory and histopathological study.

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.

Clinical and Spectrophotometric Evaluation of Skin Photoadaptation in Vitiligo Patients after a Short Cycle of NB-UVB Phototherapy.

BACKGROUND: The phenomenon of photoadaptation to narrow-band ultraviolet B (NB-UVB) radiation has been previously described in vitiligo and has usually been clinically measured by the assessment of the minimal erythema dose (MED) after phototesting. OBJECTIVES: To assess the photoadaptive response in vitiligo and healthy skin after NB-UVB phototherapy not only clinically, but also by spectrophotometry. MATERIALS AND METHODS: Fourteen patients affected by generalized vitiligo underwent NB-UVB phototherapy twice weekly for 12 weeks. Before and after phototherapy, a phototesting procedure was administered on vitiligo patches and adjacent healthy skin with a solar simulated radiation (SSR). Visual assessment of the MED took place after 24 h. A spectrophotometer was used to assess the a* value and the melanin index (MI*), as signs of skin erythema and pigmentation. The photoadaptation factor (MED-PF) and the a* photoadaptation factor (a*-PF) were calculated. RESULTS: After NB-UVB phototherapy, both vitiligo and healthy skin showed an increase in MED and MI* values and a reduction of skin erythema compared to baseline (p < 0.05). MED-PF data showed a photoadaptation in 10 (71.4%) vitiligo lesions and in 12 (85.7%) healthy skin areas. The assessment of the a*-PF showed a negative mean percentage value in all affected and unaffected skin areas. CONCLUSIONS: A short cycle of NB-UVB phototherapy can induce photoadaptation in vitiligo by increasing the MED and reducing skin erythema after stimulation with SSR. This is most likely due to the physical filter function induced by ultraviolet radiation.

Photoinduced dermatitis and oral lichenoid reaction in a chronic myeloid leukemia patient treated with imatinib mesylate.

BACKGROUND: Imatinib mesylate (IM) is a phenylaminopyrimidine that represents the first-line treatment for chronic myeloid leukemia (CML), Philadelphia chromosome-positive. It acts as a potent and selective inhibitor of the bcr-abl fusion protein by a competitive inhibition at the adenosine triphosphate-binding site of the enzyme, which leads to the inhibition of tyrosine phosphorylation of the proteins involved in bcr-abl signal transduction. IM is generally well tolerated and usually provokes only mild side effects consisting of nausea, myalgia, edema and muscle cramps. OBSERVATION: This is a report of a patient affected by CML, who developed a photoinduced dermatitis and an oral lichenoid reaction associated with IM treatment. The lesions were resolved, thanks to the withdrawal of the therapy, and they relapsed after the reintroduction of IM, confirming the drug-induced pathogenesis. CONCLUSION: Skin changes are the most common non-hematologic side effects to IM treatment and are usually dose dependent. In particular, patients with IM therapy reported a lightening and depigmentation of the skin, that may alter the skin protection against ultraviolet exposure, with a possible subsequent intolerance to sun exposure, as reported in our patient, and higher risk of skin cancer. They are frequently self-limited or easily managed; nevertheless, in some cases, the therapy needs to be discontinued or may only be continued with concomitant oral steroid.

Neoplastic and inflammatory skin disorders and serum levels of polychlorinated biphenyls in a population living in a highly polluted area.

BACKGROUND: Although polychlorinated biphenyls (PCBs) have been classified as human carcinogens for their association with melanoma, few data are available for other skin lesions. OBJECTIVES: To investigate the prevalence of skin disorders in a highly PCB polluted area in northern Italy, with locally produced food as the main source of human contamination, and evaluate the association between skin lesions and PCB serum levels, taking account of possible confounders. MATERIALS & METHODS: Thirty-three PCB congeners were quantitatively assessed and a total of 189 subjects were equally divided into three groups using the tertiles of total PCB serum concentrations. All subjects underwent a clinical examination and were interviewed on their risk factors and history of skin diseases. RESULTS: No statistically significant difference was found in the prevalence of skin cancer, nevi, pigmentary disorders as well as inflammatory and infectious skin diseases among the three PCB exposure groups. It should be noted that the use of questionnaires to assess subjects' past sun exposure and photoprotection is intrinsically flawed due to random error. CONCLUSION: Our study does not support the hypothesis that chronic PCB exposure, through the ingestion of contaminated food, determines an increased risk of developing skin diseases.

Multidisciplinary focus on methotrexate in psoriatic disesase.

The aim of this focus is to establish the role of methotrexate (MTX) in the treatment of psoriatic disease (PD). Despite the lack of hard evidence, MTX can be regarded as the nonbiological drug of choice for the treatment of peripheral psoriatic arthritis, although its effect on psoriatic dactylitis, enthesitis, and spondylitis needs to be further studied by means of well conducted clinical trials. MTX is effective in improving the skin involvement of PD, and can be used in moderate to severe psoriasis before starting a biological agent. Although rheumatologists consider it relatively safe in PD, dermatologists are very concerned about its toxicity and so, until more definite data are available, precautions should be taken to prevent MTX-induced liver fibrosis and cirrhosis.

Prevalence and risk factors of actinic keratosis in patients attending Italian dermatology clinics.

Actinic keratosis (AK) is a common keratinocyte intra-epidermal neoplasia. To assess AK prevalence and potential risk factors in patients attending Italian general dermatology clinics. This retrospective study was conducted on clinical data from consecutive white outpatients aged ≥30 years, attending 24 general dermatology clinics between December 2014 and February 2015. AK prevalence (entire population) and multivariate risk factor analysis (patients with current/previous AK and complete data) are presented. AK prevalence in 7,284 patients was 27.4% (95% CI: 26.4-28.4%); 34.3% in men and 20.0% in women (p<0.001). Independent AK risk factors in 4,604 patients were: age (OR: 4.8 [95% CI: 3.5-6.5] for 46-60 years, increasing with older age to OR: 41.5 [95% CI: 29.5-58.2] for >70 years), history of other non-melanoma skin cancers (OR: 2.7 [2.2-3.3]), residence in southern Italy/Sardinia (OR: 2.6 [2.1-3.0]), working outdoors >6 hours/day (OR: 1.9 [1.4-2.4]), male gender (OR: 1.7 [1.4-2.0]), facial solar lentigos (OR: 1.6 [1.4-1.9]), light hair colour (OR: 1.5 [1.2-1.8]), prolonged outdoor recreational activities (OR: 1.4 [1.2-1.7]), light eye colour (OR: 1.3 [1.1-1.6]), skin type I/II (OR: 1.3 [1.1-1.6]), and alcohol consumption (OR: 1.2 [1.0-3.3]). BMI ≥25.0 (OR: 0.6 [0.5-0.7]), regular sunscreen use (OR: 0.7 [0.6-0.8]), and a lower level of education (OR: 0.8 [0.7-1.0]) were independent protective factors. AK prevalence was high in Italian dermatology outpatients. We confirm several well-known AK risk factors and reveal possible novel risk and protective factors. Our results may inform on the design and implementation of AK screening and educational programmes.

A randomized split-face clinical trial analyzing daylight photodynamic therapy with methyl aminolaevulinate vs ingenol mebutate gel for the treatment of multiple actinic keratoses of the face and the scalp.

INTRODUCTION: Daylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs). The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB. METHODS: Two symmetrical contralateral areas of 25cm2, harboring a similar (5-10) number of AKs, were selected and randomly assigned either to a 3days' IMB treatment cycle or to a single session of dlPDT. The day after the local skin reaction (LSR) score was registered. Patients' scored pain (assessed through VAS method) after the treatment, and time needed for wound closure, were subsequently registered. After 90days, the complete remission (CR) rate recorded for both single lesions and patients, the cosmetic outcome and the patients' preference, were assessed. RESULTS: 22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55±1.82 with IMB and 2.05±0.72 with dlPDT (p<0.01). The mean LSR score was 9.91±4.24 and 4.59±4.03 (p<0.01), respectively. The mean days necessary for wound closure were 9.45±3.51 and 4.36±1.18days (p<0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p=NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment. CONCLUSIONS: A 3days' treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients' preference.