Cutavirus Infection in Large-Plaque Parapsoriasis, a Premalignant Condition of Mycosis Fungoides.

BACKGROUND: Cutavirus (CuV) is associated with mycosis fungoides; however, the CuV status in parapsoriasis en plaques (PP), a premalignant inflammatory condition of mycosis fungoides, has not been fully delineated. METHODS: Fifty-five Japanese patients with chronic inflammatory skin diseases, including 13 patients with PP, were studied. RESULTS: CuV DNA was detected significantly more frequently in biopsies of the lesional skin from patients with PP (38%; 4 of 13) than in those from patients with other inflammatory skin diseases (2%; 1 of 42; P = .009). All CuV-positive PP cases were of the large-plaque parapsoriasis (LPP) subtype. The viral loads ranged from 83 450 to 2 164 170 copies/103 cells. We recovered near-full-length CuV sequences from the CuV-positive LPP biopsies, all of which were of the Japanese/Asian genotype. The CuV genome appeared to be present within lymphoid cells infiltrating the epidermis and dermis. CuV NS1 and VP1 gene transcripts were also detected in the affected tissues. CONCLUSIONS: The detection of high levels of CuV DNA with the expression of viral mRNA suggests a potential role for CuV in the pathogenesis of LPP, making it necessary to study further the impact of CuV, especially regarding the viral genotype, on the outcomes of patients with CuV-positive LPP.

Prevalence, tropism, and activity of cutavirus in circulating blood lymphocytes, stool, and skin biopsy specimens of patients with cutaneous T-cell lymphoma and parapsoriasis en plaques.

A significant association has been established between a newly emerging human parvovirus, cutavirus (CuV), and cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) and its precursor parapsoriasis en plaques (PP). CTCL is a heterogeneous group of skin malignancies of T cells, the cause of which remains unknown. This study aimed to determine the activity, spread, and cell tropism of the skin-persistent CuV. CuV DNA was detected in both skin biopsies (6/20, 30%) and peripheral blood mononuclear cells (PBMCs) (4/29, 13.8%) from 49 CTCL/MF or PP patients, while none from 33 patients with any other type of skin disease or healthy subjects harbored CuV DNA. CuV DNA persisted in the skin or PBMCs for up to 15 years, despite circulating CuV-specific IgG. Spliced CuV mRNA was expressed in skin, indicating viral activity. Also, both of two available stool samples contained encapsidated CuV genomes, suggesting that the patients excrete infectious virus into the environment. Finally, CuV was observed to target circulating and skin-resident CD4 + T cells and some skin keratinocytes and macrophages. This is especially intriguing as malignant T cells in CTCL develop from CD4 + T cells. Hence, CuV should be further investigated for the overall role it plays in the complex tumor microenvironment of CTCL/MF.

Critical Review-A Tribute to Louis Brocq Lymphomatoid Papulosis, the Key in Exploring the Relationship of Parapsoriasis and Mycosis Fungoides.

ABSTRACT: Both parapsoriasis and LyP appear clinically as inflammatory dermatoses with a paradoxical link to cMF. A key element in addressing the relationship of parapsoriasis and MF were the results of the French and Dutch long-term registries tracking the emergence of lymphomas in the setting of LyP. Both cMF and cALCL emerged almost equally in these long-term studies. This ultimately supports that the stem cells in both cMF and cALCL are probably derived from a common stem cell shared by CD4+/CD8+ memory stem cells defining cMF and CD30+ stem cells defining cALCL. The discovery of inducible Skin Associated Lymphoid Tissue (iSALT) mesenchymal hubs incorporating Tregs, with their pleiotropic functions represents a paradigm shift and formed a translational tool in this analysis of the paradox. LyP can be recast as activated inhibitory lymphomatoid T-cell hubs derived from inducible iTregs in iSALT and the source of the common stem cell LyP line. iSALT Treg integrated mesenchymal hubs provided an emerging translational tool in redefining integrated lymphomatoid pathways. Brocq's complex scheme defining parapsoriasis as hybrid inflammatory dermatoses with a paradoxical link to cMF became a template to preserve parapsoriasis as a clinical diagnosis. Two major iSALT Treg generated inhibitory integrated lymphomatoid hubs emerged. The major CD30+TNF lymphomatoid hub has been linked to cALCL. Clinically defined chronic regressing and relapsing parapsoriasis with the histopathology of patch stage MF can be redefined as lymphomatoid parapsoriasis. This twin inhibited oncogenic memory based hub is defined by Treg modulated, CD4+/CD8+memory linked PD-1/DL-1 cytoxic complex and lichenoid histopathology.

Significant Association of Cutavirus With Parapsoriasis en Plaques: High Prevalence Both in Skin Swab and Biopsy Samples.

Cutavirus (CuV) is associated with cutaneous T-cell lymphoma (CTCL), of which parapsoriasis is a precursor. Our study reveals a significantly higher CuV-DNA prevalence in skin swabs of parapsoriasis patients (6/13; 46.2%) versus those of healthy adults (1/51; 1.96%). Eight patients (8/12; 66.7%) had CuV DNA in biopsied skin, and 4 developed CTCL.

Cell adhesion molecule 1 expression in mycosis fungoides versus parapsoriasis versus inflammatory dermatosis: an immunohistochemical comparative study.

Cell adhesion molecule 1 (CADM1) is one of the immunoglobulin super family adhesion molecules, that is proposed to contribute in the pathogenesis of various types of cutaneous T-cell lymphoma, including mycosis fungoides (MF). In this work, we decided to examine the immunohistochemical expression of CADM1 in MF specimens compared to premycotic parapsoriasis, benign inflammatory dermatosis and normal control skin specimens. 125 participants were enrolled (50 MF, 25 parapsoriasis, 25 inflammatory dermatosis, and 25 healthy controls). Patients were selected from the Outpatient Clinic of Dermatology and Venereology Department, Tanta University Hospitals. From all, 4 mm punch skin biopsies were taken and examined for CADM1 immunohistochemical expression. The current study revealed statistically significant upregulation of CADM1 expression in MF specimens in comparison to parapsoriasis, inflammatory dermatosis, and normal control specimens. Additionally, there was statistically significant positive correlation between CADM1 expression and progression of TNMB staging of MF disease. Therefore, it is possible to recommend CADM1 as a beneficial diagnostic immunohistochemical marker for differentiation between early stages of MF and both the premycotic parapsoriasis and benign inflammatory dermatosis. Moreover, it may be of value in early detection of neoplastic transformation of parapsoriasis as well as in assessment of MF progression.

From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis.

Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1-22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them.

Shall we exclude parapsoriasis from the medical vocabulary?

Since the first description of parapsoriasis more than 100 years ago, parapsoriasis has been a questionable condition and occasionally considered a precursor of cutaneous lymphoma. The name "parapsoriasis" is related to a heterogenous group of diseases that show a distinct clinical presentation; however, the histopathological criteria are not strongly specific. Pathologists do not consider parapsoriasis as a possible histopathological diagnosis, but dermatologists use the term as clinical hypothesis. We aim to provide an historical review of parapsoriasis focusing on histopathological criteria, considering its possible relation with cutaneous skin lymphoma, based on articles from PubMed and standard dermatopathological books. Parapsoriasis does not have well-defined histopathological criteria, so its use should be avoided. Being aware of parapsoriasis complexity, a consensus meeting can help to create a guideline regarding this topic.

Poikilodermatous Mycosis Fungoides: Comparative Study of Clinical, Histopathological and Immunohistochemical Features.

BACKGROUND: Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma. OBJECTIVES: Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation. METHODS: Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF). RESULTS: Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mix-pMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mix-pMF). DISCUSSION: This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.

[Current possibilities of the differential diagnosis of plaque parapsoriasis and the early stages of mycosis fungoides]. / Sovremennye vozmozhnosti differentsial'noi diagnostiki bliashechnogo parapsoriaza i rannikh stadii gribovidnogo mikoza.

Mycosis fungoides (MF) is the most common primary cutaneous epidermotropic T-cell lymphoma (80%). The accurate diagnosis of MF confirmed only by clinical, histological and immunohistochemical signs amounts to 50-75%. OBJECTIVE: To investigate genetic markers (FOXP3, STAT4, IL-12B) for the early diagnosis of MF, to estimate the informative value of used diagnostic techniques (histology, immunophenotyping), and to determine clonality by the T-cell receptor γ-chain genes. MATERIAL AND METHODS: Fifty patients with MF and plaque parapsoriasis (PP) who had been treated at the V.A. Rakhmanov Clinic of Skin and Venereal Diseases and at the National Medical Research Center for Hematology were followed up. A MF group consisted of 27 patients; a PP group included 23 patients, and a control group comprised 10 healthy individuals. The expression of the FOXP3, STAT4, and IL-12B genes was analyzed by TaqMan real time-PCR. The objectives of the study were affected skin portions from patients with MF or PP and healthy individuals. RESULTS: The investigation revealed a increase in the expression level of STAT4 mRNA transcripts by 9 times in patients with MF compared with those with PP and by 553 times in healthy individuals. There was also a statistically significant predominance of the expression level of STAT4 mRNA transcripts in patients with spotted and plaque stages of MF (180; 318) compared with those with PP and healthy individuals, as well as a sharp decrease in those with erythrodermic MF, which was statistically significant. CONCLUSION: MF cannot be diagnosed without comprehensively assessing the clinical, anamnestic, histological, immunophenotypic, and molecular genetic data. The expression level of STAT4 mRNA transcripts is of great importance for the early diagnosis of MF. Inclusion of the level of STAT4 expression in the list of diagnostic signs increases the accuracy of differential diagnosis of MF and PP from 59.1 to 81.8%, respectively.

Unusual Maculopapular Rash on the Scalp of a Patient with Mediterranean Spotted Fever.

OBJECTIVE: To report a rare case of maculopapular rash on the scalp in a patient with Mediterranean spotted fever (MSF). CLINICAL PRESENTATION AND INTERVENTION: A 58-year-old woman with breast cancer and chemotherapy-induced alopecia contracted MSF. Her clinical features were typical, except for a maculopapular rash covering the scalp. The diagnosis of MSF was confirmed by immunofluorescent assay. The disease had a favorable course and the patient was discharged in good condition. CONCLUSION: The rash on the scalp described in this report enriches our knowledge on the clinical characteristics of MSF.

Blisters Induced by PUVA: A Report of 5 Cases. / Ampollas inducidas por PUVA. Presentación de 5 casos.

Blisters associated with PUVA treatments are an adverse effect of photochemotherapy that has been reported in the literature. Asymptomatic blisters appear spontaneously mainly on the lower limbs and resolve without treatment. The differential diagnoses to consider include a phototoxic reaction, pseudoporphyria, and PUVA-induced bullous pemphigoid. We describe the clinical and histologic features in 5 cases of blistering secondary to PUVA treatment. If this adverse effect is accurately diagnosed, photochemotherapy need not be interrupted, and unnecessary diagnostic procedures and additional treatments can be avoided.

Risk of venous thromboembolism in patients with mycosis fungoides and parapsoriasis: A Danish nationwide population-based cohort study.

BACKGROUND: Mycosis fungoides (MF) and parapsoriasis are characterized by malignant proliferation and chronic inflammation, which may affect the risk for venous thromboembolism (VTE). OBJECTIVES: To examine the risk for VTE in patients with MF and parapsoriasis. METHODS: We conducted a nationwide population-based cohort study in Denmark to examine the relative risk (RR) of VTE in 525 patients with MF and 634 patients with parapsoriasis compared with that in sex- and age-matched controls from the general population. RESULTS: In patients with MF, the 10-year absolute risk for VTE was 3.4% (95% confidence interval [CI], 2.0-5.4). The adjusted RRs were 2.41 (95% CI, 1.49-3.90) for VTE and 4.01 (95% CI, 2.16-7.46) for pulmonary embolism. Notably, within the first 5 years after diagnosis with MF, the RR of pulmonary embolism was increased 6.7-fold (to 6.71 [95% CI, 2.86-15.72]). Patients with parapsoriasis had a 2.7-fold increased RR of VTE (to 2.67 [95% CI, 1.32-5.40]) in the absence of other established VTE risk factors. LIMITATIONS: We had no information regarding disease stage of MF and prescribed drugs. CONCLUSION: Patients with MF and parapsoriasis had an increased RR of VTE, although the absolute risk remained low. These findings should increase awareness of comorbidities in patients with MF and parapsoriasis.

Skin Microbiome in Small- and Large-plaque Parapsoriasis.

Staphylococcal enterotoxins have been shown to promote lymphoma-associated immune dysregulation. This study examined changes in the skin microbiome of parapsoriasis compared with intact skin. Swab microbiome specimens were taken of the parapsoriasis lesions of 13 patients. Control samples were taken from contralateral healthy sides of the body. Microbiotas were characterized by sequencing the V1-V3 region of the 16S ribosomal RNA bacterial genes on the Illumina MiSeq platform. The most common genera in the microbiome data were Propionibacterium (27.13%), Corynebacterium (21.20%) and Staphylococcus (4.63%). Out of the Staphylococcus sequences, 39.6% represented S. epidermidis, with the rest including S. hominis, S. capitis and unidentified species. No significant differences were observed between the patients' parapsoriasis and contralateral healthy skin or between large- and small-plaque parapsoriasis. Notable interpersonal variation was demonstrated. These results suggest that parapsoriasis is not associated with significant alterations in the cutaneous bacterial microbiome.