Estimation of serum and tissue level of interleukin-15 (IL-15) and IL-15 receptor alpha (IL-15Rα) in mycosis fungoides before and after phototherapy: An interventional cohort study.

BACKGROUND: Mycosis fungoides (MF) is a chronic, highly recurrent cutaneous T-cell lymphoma, whose pathogenesis has not yet been fully elucidated. Interleukin-15 was previously highlighted as a viability factor for cutaneous T-cell lymphoma with previous studies shedding light on its role in pathogenesis of MF and its plausibility as a potential therapeutic target. OBJECTIVE: This study was conducted to evaluate serum and tissue expression of IL-15 and IL-15Rα in early cases of MF (IA, IB, IIA) at baseline and following phototherapy. MATERIALS AND METHODS: Fourteen early MF cases were recruited. Samples were withdrawn prior to starting phototherapy treatment and following near complete clearance of the biopsied lesion or after a maximum of 36 sessions of phototherapy. Samples were assessed for change in expression of IL-15 and IL-15 Rα levels following treatment, whose levels were compared to healthy controls. RESULTS: Serum and tissue levels of IL-15 and IL-15Rα in early MF cases were significantly higher at baseline than their levels following phototherapy treatment and higher than healthy controls. However, they dropped significantly following treatment with no statistical difference between treated cases and controls, apart from serum IL-15Rα that remained significantly elevated than controls. CONCLUSION: Interleukin-15 and its receptor alpha appear to contribute to the pathogenesis of MF, being significantly elevated than healthy controls, which were normalized following phototherapy treatment, apart from serum IL-15Rα, which remained elevated. Controlling IL-15/IL-15Rα expression is a newly proposed mechanism of action of phototherapy in MF.

Assessment of tissue E-cadherin and its proteolytic serum fragment in pemphigus vulgaris before and after remission: A case-control study.

BACKGROUND: E-cadherin is a classic cadherin that mediates keratinocyte adhesion. AIMS: To assess the tissue expression of E-cadherin and its proteolytic serum fragment (soluble E-cadherin) in pemphigus vulgaris (PV) before and after clinical remission compared with controls. PATIENTS: Thirty-seven PV patients and thirty controls were enrolled. Pemphigus disease area index (PDAI) was calculated for patients at baseline and after remission. Punch biopsy specimens were taken from patients before, and after remission, and from controls for assessment of tissue E-cadherin by immunofluorescence. Similarly, serum samples were collected for assessment of serum soluble E-cadherin by ELISA. RESULTS: Presence, intensity, and mean intensity of tissue E-cadherin were significantly reduced in PV patients before treatment compared with controls (p < 0.001). Detected E-cadherin showed mainly a basal and suprabasal distribution with cell surface and a cytoplasmic expression. Serum E-cadherin was significantly higher in patients before treatment compared with controls (p = 0.006). With remission, tissue E-cadherin presence, intensity, mean intensity, and serum E-cadherin showed statistically significant improvement (p = 0.003, <0.001, <0.001, and 0.003 respectively). Tissue E-cadherin presence and serum E-cadherin level reached values equivalent to the controls (p = 0.49 and 0.44, respectively). CONCLUSIONS: Disruption of tissue E-cadherin and upregulation of serum soluble E-cadherin can contribute to the pathogenesis of PV. Clinical remission of PV is associated with normalization of tissue and serum E-cadherin.

Hypopigmented lesions in pityriasis lichenoides chronica patients: Are they only post-inflammatory hypopigmentation?

BACKGROUND/OBJECTIVES: Pityriasis lichenoides chronica (PLC) lesions are reported to subside with post-inflammatory hypopigmentation (PIH); hence, the most widely perceived nature of hypopigmented macules in PLC is PIH. However, to the best of our knowledge, no studies describing histopathological findings in these lesions are reported in literature. The aim of this study is to evaluate the hypopigmented lesions encountered in PLC patients and to shed light on their histopathological features. METHODS: A cross-sectional observational study included twenty-one patients with PLC recruited in a period of twelve months. Clinical characteristics of each patient were collected. A skin biopsy from hypopigmented lesions whenever present was taken and assessed with routine haematoxylin and eosin stain. RESULTS: Seventeen patients (81%) were less than 13 years old. Most patients (85.7%) demonstrated diffuse distribution of lesions. Hypopigmented lesions were present on the face in 12 (57.14%) patients. Histopathologically, hypopigmented lesions showed features of post-inflammatory hypopigmentation in 19% of patients, residual PLC in 52.4% and active PLC 28.6% of patients. CONCLUSION: Hypopigmented lesions in PLC were noted mainly in younger ages, histopathologically they may show features of active or residual disease, beyond post-inflammatory hypopigmentation. Consequently active treatment for patients presenting predominantly with hypopigmented lesions could be required to control the disease.

Cutaneous lymphomas and COVID-19: What is known so far?

The Coronavirus disease 2019 (COVID-19) pandemic spreads quickly all over the world. There are no sufficient data in the literature about COVID-19 infection and cutaneous lymphomas. This review sheds the light on what is known so far about COVID-19 with a cutaneous lymphoma perspective. Cutaneous T-cell lymphoma (CTCL) diagnosis does not represent a predisposing factor to viral infections and most of CTCL patients have indolent disease. However, physicians should be cautious with patients with aggressive primary cutaneous lymphomas and advanced CTCL. Different treatment strategies for cutaneous lymphomas should be taken into consideration during the COVID-19 pandemic. Thus, it is highly needed to estimate the benefit-to-risk ratio on a case-by-case basis.

HCN Channel Activity Balances Quiescence and Proliferation in Neural Stem Cells and Is a Selective Target for Neuroprotection During Cancer Treatment.

Children suffering from neurologic cancers undergoing chemotherapy and radiotherapy are at high risk of reduced neurocognitive abilities likely via damage to proliferating neural stem cells (NSC). Therefore, strategies to protect NSCs are needed. We argue that induced cell-cycle arrest/quiescence in NSCs during cancer treatment can represent such a strategy. Here, we show that hyperpolarization-activated cyclic nucleotide-gated (HCN) ion channels are dynamically expressed over the cell cycle in NSCs, depolarize the membrane potential, underlie spontaneous calcium oscillations and are required to maintain NSCs in the actively proliferating pool. Hyperpolarizing pharmacologic inhibition of HCN channels during exposure to ionizing radiation protects NSCs cells in neurogenic brain regions of young mice. In contrast, brain tumor-initiating cells, which also express HCN channels, remain proliferative during HCN inhibition. IMPLICATIONS: Our finding that NSCs can be selectively rescued while cancer cells remain sensitive to the treatment, provide a foundation for reduction of cognitive impairment in children with neurologic cancers.

PUVA-induced pityriasis lichenoides chronica-like papular lesions in patients with mycosis fungoides: a clinical, histopathological and immunohistochemical study.

Mycosis fungoides (MF) is the most common form of cutaneous T cell lymphoma (CTCL) with many clinical variants including papular and pityriasis lichenoides chronica (PLC)-like variants. During psoralen and ultraviolet A (PUVA) treatment of MF, PLC-like papular lesions were observed to appear. The exact nature of these lesions is not fully understood. This work aimed to study PLC-like papular lesions arising in MF patients receiving PUVA therapy clinically, histopathologically and immunohistochemically (using monoclonal antibodies against CD4 and CD8) and to compare them with lesions in classic PLC patients. Fifteen MF patients with PLC-like papular lesions arising during PUVA treatment were included and 15 patients with classic PLC served as controls. While the extent of these lesions significantly correlated with their duration (p < 0.05), it showed no significant correlation with the TNMB stage of MF, number of phototherapy sessions or cumulative UVA dose at which they started to appear. The response status of MF to PUVA did not affect their development. Compared to classic PLC, these lesions showed significantly more acute onset (p = 0.003). None of these lesions showed histopathological features essential to diagnose papular/PLC-like MF and no significant difference existed with regard to their histopathological and CD4/CD8 phenotypic features compared to classic PLC. Papular lesions mimicking PLC in MF patients receiving PUVA mostly represent an upgrading reaction with possible good prognostic implication.

Hypopigmented Interface T-Cell Dyscrasia and Hypopigmented Mycosis Fungoides: A Comparative Study.

Hypopigmented interface T-cell dyscrasia (HITCD) is a distinct form of lymphoid dyscrasia that may progress to hypopigmented mycosis fungoides (HMF). We compared both diseases as regards their CD4/CD8 phenotype and expression of granzyme B and tumor necrosis factor-alpha (TNF-α) and how these are affected by narrow-band UVB (nb-UVB). The study included 11 patients with HITCD and 9 patients with HMF. They received nb-UVB thrice weekly until complete repigmentation or a maximum of 48 sessions. Pretreatment and posttreatment biopsies were stained using anti CD4, CD8, TNF-α, and granzyme B monoclonal antibodies. Epidermal lymphocytes were CD8 predominant in 54.5% and 66.7% of HITCD and HMF cases, respectively, whereas dermal lymphocytes were CD4 predominant in 63.6% and 66.7%, respectively. Significantly, more dermal infiltrate was encountered in HMF (P = 0.041). In both diseases, granzyme B was only expressed in the dermis, whereas TNF-α was expressed both in the epidermis and dermis. No difference existed as regards the number of sessions needed to achieve repigmentation or cumulative nb-UVB dose reached at end of study. (P > 0.05). Narrow-band UVB significantly reduced only the epidermal lymphocytes in both diseases (P ≤ 0.05) with their complete disappearance in 8 (72.7%) HITCD and 6 (66.7%) HMF cases. In both diseases, nb-UVB did not affect granzyme B or TNF-α expression (P > 0.05). In conclusion, both diseases share the same phenotype, with HITCD being a milder form of T-cell dysfunction. In both diseases, epidermal lymphocytes are mainly CD8-exhausted cells lacking cytotoxicity, whereas dermal cells are mostly reactive cells exerting antitumor cytotoxicity. Tumor necrosis factor-alpha mediates hypopigmentation in both diseases and prevents disease progression. Repigmentation after nb-UVB in both diseases occurs before and independently from disappearance of the dermal infiltrate.

Phototherapy: The vitiligo management pillar.

Phototherapy has been the mainstay of vitiligo therapy for several decades. A variety of wavelengths and modalities are available, but narrowband ultraviolet B remains the safest and most commonly used treatment. Acting on multiple steps in vitiligo pathogenesis, narrowband ultraviolet B is one of the few therapies that can effectively induce stabilization and stimulate repigmentation. Achievement of optimal results involves using a combination of appropriate treatment protocols, careful patient selection, and patient education to set expectations. Individual patient characteristics, including disease activity, vitiligo phenotype, lesion location, and skin phototype, should all be considered, along with combination therapies.

Phototherapeutic modalities pose no significantly increased risk of oxidative damage to DNA in dark skinned individuals.

BACKGROUND: 8-oxoguanine, a major product of DNA oxidation, is considered a key parameter in measuring the carcinogenic effects of ultraviolet radiation. OBJECTIVE: To assess and compare the carcinogenic potential of different photo (chemo) therapeutic modalities in photoresponsive skin diseases by measuring the levels of 8-oxoguanine in dark-skinned individuals before and after photo (chemo) therapy. METHODS: A prospective, randomized controlled pilot study was conducted in 63 patients of skin types III-V with photo-responsive dermatoses including vitiligo, psoriasis and mycosis fungoides. Patients were divided into three groups; Group 1 (received narrowband ultraviolet-B), Group 2 (received psoralen plus ultraviolet-A) and Group 3 (received broadband ultraviolet-A). Biopsies were taken before and after phototherapy to measure 8-oxoguanine levels using enzyme-linked immunosorbent assay. Biopsies were also taken from the sun-protected skin in 21 controls subjects who had no dermatological disease. RESULTS: Regardless of the disease, a significantly higher level of 8-oxoguanine was found after treatment when compared to the pre-treatment baseline levels; however, these levels were comparable to those in control subjects. A weakly significant positive correlation was found between cumulative dose and 8-oxoguanine levels following psoralen plus ultraviolet-A therapy. In controls, comparing the 8-oxoguanine levels between skin types III and IV showed significantly lower 8-oxoguanine in skin type IV. CONCLUSION: Therapeutic doses of ultraviolet radiation are relatively safe in dark skinned patients; however, minimizing the cumulative dose of phototherapeutic modalities (particularly psoralen plus ultraviolet-A) is recommended.

BB-UVA vs. NB-UVB in the treatment of vitiligo: a randomized controlled clinical study (single blinded).

BACKGROUND: Vitiligo is an acquired pigmentary disorder that affects between 1% and 2% of the general population. Phototherapy remains the cornerstone of treatment, with NB-UVB being the most frequently used. BB-UVA can be a plausible alternative for darker population; skin photo type III and IV. PATIENTS AND METHODS: The study was a prospective, randomized, controlled, and single-blinded clinical trial, conducted on 40 patients with bilateral symmetrical vitiligo. The patients were randomly divided into two equal groups; group (A) received a fixed dose of 15 J/cm(2) BB-UVA, while group (B) received NB-UVB. The study was conducted for a period of 16 weeks (48 sessions). RESULTS: The final percentage of clinical improvement was significantly higher (P = 0.047) within the BB-UVA group (63.82% ± 27.42), than within the NB-UVB group (44.32% ± 29.78). CONCLUSION: BB-UVA can be considered as an alternative treatment line for vitiligo.

ISPCAN Child Abuse Screening Tools Retrospective version (ICAST-R): Delphi study and field testing in seven countries.

OBJECTIVES: To gain consensus among an ethnically and linguistically diverse group of international child protection experts on the structure and content of a new survey tool for retrospective measurement of child abuse, and to determine the performance of the instrument through an international field trial with young adults. METHODS: The questionnaire was developed through focus group discussions with international experts, and then subjected to a Delphi study in two waves to determine the perceived importance and translatability of items. The resultant questionnaire was translated into six languages and field tested in seven countries with convenient samples of young adults aged 18-26 years (N=842). RESULTS: Child maltreatment experts from 28 countries provided input to questionnaire development. Satisfactory agreement on draft item inclusion and exclusion and the translatability of items was gained. The tool includes 15 primary questions about potentially abusive physical, sexual and emotional events, with follow-up questions about perpetrator characteristics, frequency of acts and periods in childhood when the recalled abuse occurred. The field test revealed lifetime prevalence per item usually exceeded 10% (11/15 items; range 2.1-49.5%). Internal consistency (Cronbach's alpha) was moderate to high for each of three item sub-sets (between .61 and .82) and the rates of missing data were low (less than 1.5% for 14 of 15 items). The great majority of respondents nominated either peer and/or adult perpetrators (between 82.3% and 98.2% depending upon the item), and among these, child/adolescent peers and non-family adults (including teachers for emotional and physical acts) were nominated often. CONCLUSIONS: The ICAST-R is based on consensus from international experts, translates clearly and has satisfactory properties for adoption as a survey tool to estimate prevalence and describe perpetrators and other contextual aspects of child abuse. PRACTICE IMPLICATIONS: This tool can be utilized in a broad range of cultures and languages and may contribute to improved research practice. Although the core items are limited to just 15 acts of maltreatment, if these behaviorally specific questions are adopted as key indicators and incorporated into comprehensive local, national or regional surveys, eventually there should be greater comparability in survey estimates.

The development and piloting of the ISPCAN Child Abuse Screening Tool-Parent version (ICAST-P).

OBJECTIVE: Child maltreatment is a problem that has longer recognition in the northern hemisphere and in high-income countries. Recent work has highlighted the nearly universal nature of the problem in other countries but demonstrated the lack of comparability of studies because of the variations in definitions and measures used. The International Society for the Prevention of Child Abuse and Neglect has developed instrumentation that may be used with cross-cultural and cross-national benchmarking by local investigators. DESIGN AND SAMPLING: The instrument design began with a team of expert in Brisbane in 2004. A large bank of questions were subjected to two rounds of Delphi review to develop the fielded version of the instrument. Convenience samples included approximately 120 parent respondents with children under the age of 18 in each of six countries (697 total). RESULTS: This paper presents an instrument that measures parental behaviors directed at children and reports data from pilot work in 6 countries and 7 languages. Patterns of response revealed few missing values and distributions of responses that generally were similar in the six countries. Subscales performed well in terms of internal consistency with Cronbach's alpha in very good range (0.77-0.88) with the exception of the neglect and sex abuse subscales. Results varied by child age and gender in expected directions but with large variations among the samples. About 15% of children were shaken, 24% hit on the buttocks with an object, and 37% were spanked. Reports of choking and smothering were made by 2% of parents. CONCLUSION: These pilot data demonstrate that the instrument is well tolerated and captures variations in, and potentially harmful forms of child discipline. PRACTICE IMPLICATIONS: The ISPCAN Child Abuse Screening Tool - Parent Version (ICAST-P) has been developed as a survey instrument to be administered to parents for the assessment of child maltreatment in a multi-national and multi-cultural context. It was developed with broad input from international experts and subjected to Dephi review, translation, and pilot testing in six countries. The results of the Delphi study and pilot testing are presented. This study demonstrates that a single instrument can be used in a broad range of cultures and languages with low rates of missing data and moderate to high internal consistency.

Different narrowband UVB dosage regimens in dark skinned psoriatics: a preliminary study.

BACKGROUND: Psoriasis is a common and relapsing disease, which is both physically and psychologically disabling. Narrowband UVB (NB-UVB) is used in fair-skinned population in suberythemogenic doses with good results; however, in the darker skin population (skin types III, IV, V) erythemogenic doses have not been thoroughly investigated. AIM: A left-right bilateral comparative trial was carried out to compare the suberythemogenic dose of NB-UVB vs. erythemogenic dose in the treatment of dark-skinned psoriatic patients. PATIENTS AND METHODS: The study was conducted on 20 patients with chronic plaque psoriasis. The left side was treated with the dose causing minimal erythema [100% of minimal erythema dose (MED)] while the right side received 70% of this MED (suberythemogenic side). RESULTS: Our results revealed no statistically significant difference in PASI final and in the percentage of reduction of PASI score between both sides as well as the total number of sessions (P-value>0.05), while the total cumulative UVB dose on the suberythemogenic side was significantly lower (P-value<0.001). CONCLUSION: Our study recommends reducing the dose regimen of NB-UVB and consequently the cumulative UVB dose by using the suberythemogenic dosing schedule even in dark skin population.

Ultraviolet A in vitiligo.

Both types of Ultraviolet (UV), UVB (290-320 nm) and UVA (320-400 nm), produce increased pigmentation or tanning. However, no evaluation of UVA alone in the treatment of vitiligo has been reported. Therefore, it was the purpose of this work to study the pigmentogenic effect of UVA (5 and 15 J/cm(2)) in vitiligo. The study included 20 randomly selected patients with vitiligo involving more than 30% of the body surface area with a bilateral/symmetrical distribution. They were equally divided into two groups each of 10 patients. All patients received three weekly sessions of UVA, 15 J/cm(2) in group I and 5 J/cm(2) in group II, a total of 48 sessions over 16 weeks. Overall pigmentation of 60% and above was recorded in 50% and 10% of patients in groups I and II, respectively. We conclude that broadband UVA alone, without psoralens, and in appropriate doses may be of important therapeutic value in vitiligo.

Role of apoptosis stimulus factor and its ligand in the induction of apoptosis in some ultraviolet induced diseases.

BACKGROUND: Fas (factor of apoptosis stimulus) is one of the death receptors belonging to the tumor necrosis factor superfamily of receptors. When bound to its ligand, Fas-ligand (Fas-L), it triggers apoptosis. Ultraviolet (UV) rays can induce keratinocyte apoptosis by Fas/Fas-L interaction. AIM: The aim of the study was to evaluate the role of Fas and Fas-L in basal cell carcinoma (BCC) as an example of malignant neoplasm and discoid lupus erythematosus (DLE) as a benign skin disease, which are both induced by UV. SUBJECTS AND METHODS: The study included 20 cases of BCC, 20 cases of DLE and ten control cases. All biopsies of BCC and DLE were examined histopathologically. They were also examined for Fas and Fas-L by PCR. RESULTS: In BCC, apoptosis was detected in 60 percent of cases. Fas was found to be positive in only one case and it was found to be negative in the other 19 cases (95 %). Fas-L was found to be positive in 100 percent of cases. In DLE, apoptosis was detected in 90 percent of cases. Fas was positive in 80 percent of cases, Fas-L was positive in 90% of cases. CONCLUSION: Over-expression of Fas-L and lack of expression of Fas by tumor cells together with other factors act in favor of BCC by helping its survival and progression. Also, it seems that Fas/Fas-L interaction plays a critical role in the apoptosis seen in cases of DLE and hence in the pathogenesis of DLE.