Evaluation of Alitretinoin for the Treatment of Mycosis Fungoides and Sézary Syndrome.

BACKGROUND: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most common subtypes of cutaneous T-cell lymphoma (CTCL). There is currently no cure for CTCL, and treatment is aimed at limiting disease progression. This study evaluated the efficacy and tolerability of alitretinoin in CTCL management. METHODS: A retrospective, multicenter study was conducted on CTCL patients treated with alitretinoin as a primary agent or in combination with standard therapies. RESULTS: Forty-eight patients with MF (n = 40) and SS (n = 8) with a median age of 59.7 years (±14.3) were eligible for study inclusion. Treatment response data were evaluated in 40 patients and safety in 42 patients. 40.0% of the patients had early-stage, 43.8% had advanced-stage CTCL, and in 16.7% of patients there was insufficient information for staging. 40.0% (16/40) of the patients achieved a complete or partial response, whereas 47.5% (19/40) achieved stable disease, 12.5% (5/40) had progressive disease, and there were no cases of disease relapses in responders. Both early and advanced stages of CTCL were responsive to alitretinoin as a primary or combined modality. Alitretinoin was well tolerated, and 64.3% (27/42) of patients did not report any side effects. The most commonly observed side effect was hypertriglyceridemia. CONCLUSIONS: This retrospective analysis supports the efficacy and safety of alitretinoin in clearing skin disease and preventing disease progression in CTCL as a monotherapy or in combination with standard therapies.

Association between Prurigo Nodularis and Etiologies of Peripheral Neuropathy: Suggesting a Role for Neural Dysregulation in Pathogenesis.

Background: Prurigo nodularis (PN) is an intensely pruritic skin condition of considerable morbidity. However, the pathogenesis of PN and its association with underlying neuropathy is unclear. Objective: We sought to investigate the association between PN and etiologies of peripheral neuropathy. Methods: A cross-sectional analysis of adult patients (≥18-year-old) with PN, AD, and Psoriasis at the Johns Hopkins Health System over a six-year period (January 2013-January 2019) was performed. The strength of association with etiologies of peripheral neuropathy were compared to a control cohort of individuals without PN, as well as those with AD or psoriasis. Results: A total of 1122 patients with PN were compared to 10,390 AD patients, 15,056 patients with psoriasis, and a control cohort of 4,949,017 individuals without PN, with respect to 25 comorbidities associated with peripheral neuropathies. Limitations: Comparisons between peripheral neuropathies and PN represent associations but are not causal relationships. Conclusion: Prurigo nodularis is strongly associated with peripheral neuropathies, suggesting a role for neural dysregulation in pathogenesis.

Comorbidities in Mycosis Fungoides and Racial Differences in Co-Existent Lymphomatoid Papulosis: A Cross-Sectional Study of 580 Patients in an Urban Tertiary Care Center.

Background: Mycosis fungoides (MF) is a cutaneous T-cell lymphoma. Previous reports have suggested MF is associated with inflammatory conditions such as psoriasis, increased cardiovascular risk factors as well as secondary neoplasms. Methods: A cross-sectional study of MF patients seen from 2013 to 2019 was performed. Comorbidities were selected based on the 2015 Medicare report highlighting the most common chronic medical illnesses in the United States. Lifetime comorbidity occurrence in patients with MF were compared with that in patients with atopic dermatitis, psoriasis and patients without MF. Additional analyses were performed with patients sub-stratified by race. Results: Compared to control groups, MF was strongly associated with lymphomatoid papulosis and Hodgkin's disease, but not significantly associated with lung, breast or colon cancer. Interestingly, the association with lymphomatoid papulosis was observed in Caucasians (CI 1062-4338; p < 0.001) and not African Americans (p = 0.9). Patients with MF had a greater association with congestive heart failure, hypertension (HT) and hyperlipidemia (HLD) compared with the general population. However, they were significantly less likely to have HT and HLD when compared with psoriasis patients (HT CI: 0.6-0.9; p < 0.001, and HLD CI: 0.05-0.07; p < 0.001). MF patients were also significantly less likely to have concomitant vitamin D deficiency compared with atopic dermatitis (AD) and psoriasis (p < 0.001). Conclusions: Our results suggest that the association of MF with lymphomatoid papulosis varies by race. Compared to the general population, hypertension and hyperlipidemia were positively associated with MF, however, these were significantly less likely on comparison to psoriasis. Unlike previously described, vitamin D deficiency was found to be significantly less in patients with MF.

Analysis of CTCL cell lines reveals important differences between mycosis fungoides/Sézary syndrome vs. HTLV-1+ leukemic cell lines.

HTLV-1 is estimated to affect ~20 million people worldwide and in ~5% of carriers it produces Adult T-Cell Leukemia/Lymphoma (ATLL), which can often masquerade and present with classic erythematous pruritic patches and plaques that are typically seen in Mycosis Fungoides (MF) and Sézary Syndrome (SS), the most recognized variants of Cutaneous T-Cell Lymphomas (CTCL). For many years the role of HTLV-1 in the pathogenesis of MF/SS has been hotly debated. In this study we analyzed CTCL vs. HTLV-1+ leukemic cells. We performed G-banding/spectral karyotyping, extensive gene expression analysis, TP53 sequencing in the 11 patient-derived HTLV-1+ (MJ and Hut102) vs. HTLV-1- (Myla, Mac2a, PB2B, HH, H9, Hut78, SZ4, Sez4 and SeAx) CTCL cell lines. We further tested drug sensitivities to commonly used CTCL therapies and studied the ability of these cells to produce subcutaneous xenograft tumors in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice. Our work demonstrates that unlike classic advanced MF/SS cells that acquire many ongoing balanced and unbalanced chromosomal translocations, HTLV-1+ CTCL leukemia cells are diploid and exhibit only a minimal number of non-specific chromosomal alterations. Our results indicate that HTLV-1 virus is likely not involved in the pathogenesis of classic MF/SS since it drives a very different pathway of lymphomagenesis based on our findings in these cells. This study also provides for the first time a comprehensive characterization of the CTCL cells with respect to gene expression profiling, TP53 mutation status, ability to produce tumors in mice and response to commonly used therapies.