Paediatric Mycosis Fungoides: Clinical Variants, Treatment Modalities and Response to Therapy.

Mycosis fungoides is a rare cutaneous lymphoma in the paediatric population. The aim of this study was to examine the epidemiological, clinical, and histological characteristics, as well as the treatment modalities and response to therapy of paediatric patients with mycosis fungoides. This retrospective cohort study reviewed the records of 37 paediatric patients treated at Rambam Medical Center, Israel, between 2013 and 2021. Extracted data included epidemiology, clinical presentation, histological reports, infiltrate clonality status, treatment modalities and response to therapy. The mean follow-up period was 60 months. All patients were diagnosed with stage IA or IB disease. Folliculotropic mycosis fungoides was the most prevalent variant (49%). Most patients were treated with phototherapy (90%), with a response rate of 85%, and a complete response rate of 55% after the first course. There were no significant differences in response to phototherapy between the folliculotropic or other variants (p = 0.072). Similarly, delayed diagnosis, atopic diathesis, clonality, phototherapy type or number of treatments, were not associated with response to therapy, while protracted phototherapy was associated with prolonged remission. In conclusion, mycosis fungoides in the paediatric population is an indolent disease with a favourable prognosis and potentially prolonged response to phototherapy.

The role of itch and pain modulation in the prediction of phototherapy outcomes: a prospective cohort study.

OBJECTIVES: Ability to predict which chronic itch patients will benefit from particular treatments is a challenge. Common features in itch and pain in respect to sensory elicitation, and mechanisms of processing including sensitization and inhibition at the peripheral and central levels, may serve to understand variability in treatment outcomes. As such this study aimed to explore whether phototherapy outcomes can be predicted by psychophysical parameters of pain and itch modulatory processing. METHODS: Prospective cohort study on chronic-itch patients (n = 44) assessed before 20 treatments of NB UVB. Level of itch and pain reduction following painful stimulation (reflecting the 'pain inhibits pain' phenomenon) used to assess the top-down modulation response efficacy. Magnitude of Conditioned Pain Modulation (CPM) for itch (CPM-itch) and for pain (CPM-pain) (reflecting inhibition) and magnitude of temporal summation (TS) of pain (reflecting ascending facilitation pathways) assessed to predict treatment effect. RESULTS: Higher improvement of itch symptoms following phototherapy was correlated with more efficient CPM-itch (r = 0.62, p < .001), but not magnitude of CPM-pain or level of temporal summation. DISCUSSION: Findings emphasize the role of descending inhibition pathways in determining phototherapy efficacy in chronic itch patients. Such an evaluation-based approach may contribute to better patient selection for phototherapy improving patients' disease outcomes.

Follicular Eruption With Folliculotropic Lymphocytic Infiltrates Associated With Iatrogenic Immunosuppression: Report and Study of 3 Cases, and Review of the Literature.

BACKGROUND: Several cases of folliculotropic mycosis fungoides, associated with immunosuppressive therapy, including calcineurin inhibitors, have been reported in solid organ transplant patients. We have encountered 3 patients on immunosuppressive therapy who developed follicular eruptions with folliculocentric infiltrates of nonatypical lymphocytes. OBJECTIVE: To characterize these follicular eruptions and review the literature. METHODS: Three patients, aged 7-15 years, who were treated with systemic immunosuppressive therapy developed follicular eruptions characterized histopathologically by folliculocentric lymphocytic infiltrates. These were studied clinically, histopathologically, immunophenotypically, and molecularly for T-cell receptor (TCR) gene rearrangement. RESULTS: All 3 cases were characterized histopathologically by folliculocentric infiltrates of nonatypical CD3 T lymphocytes with variable follicular exocytosis. Two cases also showed follicular mucinosis. Marked reduction in CD7 staining, and marked predominance of CD4 cells over CD8 cells was observed in all 3 cases. The TCR gene rearrangement studies were monoclonal in 2 cases. Oral calcineurin inhibitors (2 cyclosporine A and 1 tacrolimus) were part of the therapeutic regimen in all 3 patients. Their cessation along with local corticosteroid creams in 2 patients, and phototherapy with oral acitretin in one patient, was associated with complete clinical remission. CONCLUSIONS: Patients undergoing systemic immunosuppressive therapy that includes calcineurin inhibitors might develop follicular eruption with some immunophenotypical variations and a monoclonal TCR gene rearrangement but lack sufficient cytomorphological features of folliculotropic mycosis fungoides. Altering the immunosuppressive agent including calcineurin inhibitors may result in regression of the eruptions.

Insulin-like growth factor-binding protein 7 regulates keratinocyte proliferation, differentiation and apoptosis.

Insulin-like growth factor (IGF)-binding protein 7 (IGFBP7) belongs to the IGFBP superfamily, which is involved in the regulation of IGF and insulin signaling. Recently, a global gene expression study revealed that IGFBP7 is downregulated in the psoriatic epidermis, with UVB phototherapy restoring its expression to normal. In the present study, we confirmed that IGFBP7 expression is decreased in psoriatic lesions. Given the previous data suggesting a role for IGFBP7 in the control of cancer cell growth, we investigated its involvement in the regulation of keratinocyte (KC) proliferation and differentiation, which are abnormal in psoriasis. To model IGFBP7 downregulation in vitro, we used IGFBP7-specific small interfering RNA or small hairpin RNA-expressing lentiviral vectors in HaCaT cells or primary human KCs. Downregulation of IGFBP7 was found to markedly enhance KC proliferation in both systems, was associated with a significant decrease in KC susceptibility to tumor necrosis factor-alpha-induced apoptosis, but did not affect senescence. Downregulation of IGFBP7 was also shown to block expression of genes associated with calcium-induced differentiation of human KCs. Finally, recombinant IGFBP7 was found to inhibit KC proliferation and enhanced their apoptosis. These data position IGFBP7 as a regulator of KC proliferation and differentiation, suggesting a potential role for this protein in the pathophysiology and treatment of hyperproliferative dermatoses such as psoriasis.

Low dose methotrexate therapy is effective in late-onset atopic dermatitis and idiopathic eczema.

BACKGROUND: Atopic dermatitis or atopic eczema is an itchy inflammatory skin condition with a predilection of the skin flexures. Most cases start in children although some have been reported in adults. Patients with moderate to severe disease refractory to topical corticosteroid or calcineurin inhibitors may require second-line treatment such as phototherapy or systemic immunosuppressants. Methotrexate therapy has been suggested as a useful immunosuppressant in adult atopic dermatitis. OBJECTIVES: To further determine the efficacy of low dose methotrexate therapy in adults with new-onset atopic dermatitis or with idiopathic eczema. METHODS: All adult patients with new-onset atopic dermatitis or idiopathic eczema treated by methotrexate in our clinics from 2004 to 2006 were included in the study. All had failed prolonged therapy with oral antihistamines and local corticosteroid creams. Methotrexate, 10-20 mg, was given orally once a week along with folic acid supplements 5 days a week. Additional therapies included predominantly emollients. During the entire treatment period the investigators made global assessments of the clinical response. RESULTS: Nine patients diagnosed with late-onset atopic dermatitis (n = 6) or idiopathic eczema (n = 3) were treated with methotrexate. All patients responded to the drug. The initial response was noted after 3-7 weeks. Six patients achieved complete remission after 3 months of methotrexate therapy and three patients had significant improvement. One patient's condition worsened after achieving a complete response while on methotrexate and the drug was withdrawn completely. No serious adverse events were noted during treatment. CONCLUSIONS: Low dose methotrexate is an effective therapeutic alternative for late-onset atopic dermatitis or idiopathic eczema in patients unresponsive to local and other systemic therapies.