Primary Cutaneous Lymphoma Registry of the Spanish Academy of Dermatology and Venereology (AEDV): Data for the First 5 Years. / Registro de linfomas cutáneos primarios (RELCP) de la AEDV: datos tras 5 años de funcionamiento.

BACKGROUND AND OBJECTIVE: Primary cutaneous lymphomas (PCL) are uncommon. Observations based on the first year of data from the Spanish Registry of Primary Cutaneous Lymphomas (RELCP, in its Spanish abbreviation) of the Spanish Academy of Dermatology and Venereology (AEDV) were published in February 2018. This report covers RELCP data for the first 5 years. PATIENTS AND METHODS: RELCP data were collected prospectively and included diagnosis, treatments, tests, and the current status of patients. We compiled descriptive statistics of the data registered during the first 5 years. RESULTS: Information on 2020 patients treated at 33 Spanish hospitals had been included in the RELCP by December 2021. Fifty-nine percent of the patients were men; the mean age was 62.2 years. The lymphomas were grouped into 4 large diagnostic categories: mycosis fungoides/Sézary syndrome, 1112 patients (55%); primary B-cell cutaneous lymphoma, 547 patients (27.1%); primary CD30+lymphoproliferative disorders, 222 patients (11%), and other T-cell lymphomas, 116 patients (5.8%). Nearly 75% of the tumors were registered in stage I. After treatment, 43.5% achieved complete remission and 27% were stable at the time of writing. Treatments prescribed were topical corticosteroids (1369 [67.8%]), phototherapy (890 patients [44.1%]), surgery (412 patients [20.4%]), and radiotherapy (384 patients [19%]). CONCLUSION: The characteristics of cutaneous lymphomas in Spain are similar to those reported for other series. The large size of the RELCP registry at 5 years has allowed us to give more precise descriptive statistics than in the first year. This registry facilitates the clinical research of the AEDV's lymphoma interest group, which has already published articles based on the RELCP data.

Postoperative radiotherapy provides better local control and long-term outcome in selective cases of cutaneous squamous cell carcinoma with perineural invasion.

BACKGROUND: Perineural invasion (PNI) is a feature of poor prognosis in cutaneous squamous cell carcinoma (CSCC). The benefit of postoperative radiotherapy (PORT) in the management of CSCC with PNI is still not well established. OBJECTIVES: We aimed to evaluate the usefulness of PORT in the treatment of CSCC with PNI so as to determine which patients would best benefit from this type of treatment. METHODS: A retrospective multicenter cohort of 110 CSCCs with PNI was evaluated. Eighteen recurrent cases were excluded for subsequent analysis. We searched for the types of PNI associated with poor outcome and analysed the effectiveness of PORT on different groups of CSCC with PNI. We also assessed for the usefulness of PORT depending on the surgical margin status (either clear or positive). RESULTS: Postoperative radiotherapy showed clear benefit over observation in CSCC with PNI and positive margins after surgery, where the management by observation increased the risk of poor outcome events 2.43 times (P = 0.025), and especially in those with positive margins and PNI ≥0.1 mm, where the risk of poor prognosis is eight times greater following a management by observation (P = 0.0065). Multivariate competing risk analysis preserved statistical significance. CONCLUSIONS: The use of PORT on patients with CSCC with PNI and positive margins after surgery, especially in PNI ≥0.1 mm, significantly improves long-term outcome. The benefit of PORT in cases with clear margins is not as evident, especially in those with PNI of small-calibre nerves. Clinical trials are imperative.

Prognostic factors in patients with primary cutaneous anaplastic large cell lymphoma: a multicentric, retrospective analysis of the Spanish Group of Cutaneous Lymphoma.

BACKGROUND: Reliable prognostic factors for patients with primary cutaneous anaplastic large cell lymphoma (PCALCL) are lacking. OBJECTIVE: To identify prognostic factors for specific survival in patients with PCALCL. METHODS: Using the convenience sampling method, patients with PCALCL diagnosed from May 1986 to August 2017 in 16 University Departments were retrospectively reviewed. RESULTS: One hundred eight patients were included (57 males). Median age at diagnosis was 58 years. All of them showed T1-3N0M0 stages. Seventy per cent of the cases presented with a solitary lesion, mostly at the limbs. Complete response rate after first-line treatment was 87%, and no advantage was observed for any of them (surgery, radiotherapy, chemotherapy or other approaches). Nodal and visceral progression rate was 11% and 2%, respectively. 5-year specific survival (SSV) reached 93%; 97% for T1 patients and 84% for T2/T3 patients (P = 0.031). Five-year SSV for patients developing early cutaneous relapse was 64%; for those with late or no relapse, 96% (P = 0.001). Estimated median SSV for patients showing nodal progression was 103 months (95% CI: 51-155 months); for patients without nodal progression, estimated SSV did not reach the median (P < 0.001). Nodal progression was an independent predictive parameter for shorter survival (P = 0.011). CONCLUSION: Multiple cutaneous lesions at presentation, early skin relapse and nodal progression portrait worse prognosis in patients with PCALCL.

Initial results of ixekizumab efficacy and safety in real-world plaque psoriasis patients: a multicentre retrospective study.

BACKGROUND: Ixekizumab (anti-IL17A) is effective as treatment for moderate-to-severe plaque psoriasis, but real-life data on effectiveness and safety are currently very limited. OBJECTIVE: To evaluate the efficacy and safety of ixekizumab in a cohort of real-life plaque psoriasis patients. METHODS: Retrospective chart review of 100 patients with moderate-to-severe plaque psoriasis treated with ixekizumab at seven Spanish dermatological centres. RESULTS: According to the as observed analysis, the percentage of patients achieving a 75% and 90% of reduction from the baseline score of Psoriasis Area and Severity Index (PASI) was 87.5%-50.0% at week 12-16; 88.3%-58.4% at week 24 and 82.9%-58.5% at week 52, respectively. The mean ± standard deviation (SD) score of PASI at baseline was 12.9 ± 9.2, and it declined rapidly after ixekizumab administration to 1.9 ± 4.0 (P < 0.001) at week 12-16 and was maintained at 1.7 ± 4.1 and 1.8 ± 2.9 at week 24 and 52, respectively. Ixekizumab response was not affected by clinical variables like body mass index, disease duration or the presence of psoriatic arthritis. However, the bio-naive group showed significantly higher PASI 75 response rate at week 12-16 compared to patients previously exposed to biologic agents (P = 0.037). Twenty-six (26%) patients experienced adverse events (AEs) during the follow-up period, being most of them of mild-to-moderate intensity. The most common AE was local reaction at the site of injection (14/26; 53.8%). At the end of the observational period, 15 (15%) patients discontinued ixekizumab treatment due to limited clinical improvement (n = 11), adverse events (n = 3) or lost to follow-up (n = 1) within a mean ± SD time of 6.0 ± 3.9 months. CONCLUSION: The present study illustrates the initial experience with ixekizumab in real-world clinical practice confirming its usefulness and safety in the management of plaque psoriasis patients.

Synovial nerve fiber density decreases with naturally-occurring osteoarthritis in horses.

OBJECTIVE: To measure the nerve fiber density in synovial membranes from healthy and OA equine joints and to investigate the relationship between synovial innervation and OA severity, synovial vascularity and synovitis. DESIGN: Twenty-five equine metacarpophalangeal joints were collected post-mortem. The joints were dissected and the macroscopic lesions of the articular cartilage were scored. Synovial membrane specimens (n = 50) were harvested, fixed, sectioned and scored histologically. Immunohistochemical staining and immunofluorescence with S-100 protein, that identifies nerve fibers, and ⍺-actin, that stains vascular smooth muscle, were also performed on site-matched specimens and the relationships between these tissues was interrogated. RESULTS: The nerve fiber density was higher in the superficial layer (≤200 µm) of the synovium when compared to the deeper layer in control equine joints (mean difference (95% C.I.): 0.054% (0.018%, 0.11%)). In osteoarthritic joints, synovial innervation decreased in the superficial layer with increasing macroscopic OA score (ß (SEM), 95% C.I.: -0.0061 (0.00021), -0.0011, -0.00017). The blood vessel density was also higher in the superficial layer of the synovium compared to the deep layer in the control (mean difference (95% C.I.): 1.1% (0.36%, 2.3%)) and OA (mean difference (95% C.I.): 0.60% (0.22%, 1.2%)) equine joints. Moreover, considering all synovial specimens, higher nerve fiber density in the deep layer positively correlated with blood vessel density (ß (SEM), 95% C.I.: 0.11 (0.036), 0.035, 0.18). CONCLUSION: The reduction in nerve fiber density with advanced cartilage degeneration suggests that peripheral neuropathy is associated with equine OA. Whether this link is associated with neuropathic pain, requires further investigation.

First-line treatment in lymphomatoid papulosis: a retrospective multicentre study.

BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.

Transcriptome analysis of severely active chronic spontaneous urticaria shows an overall immunological skin involvement.

BACKGROUND: The knowledge about chronic spontaneous urticaria (CSU) phenotypes is based on its clinical characteristics, associated comorbidities, course of the disease, and its response to the available effective drugs. Genotype expression and its further correlation with CSU phenotypes are still unknown. We describe the cutaneous transcriptome of patients suffering a severely active CSU refractory to antihistamine treatment. METHODS: Through the bioinformatic analysis of the whole Human Genome with Oligo Microarrays and quantitative real-time polymerase chain reaction (qPCR), relevant genes expressed in nonlesional (NLS-CSU) and lesional skin (LS-CSU) and peripheral blood were identified in 20 patients suffering from severely active CSU and 10 healthy controls (HCs). RESULTS: From 39 genes differentially expressed in NLS-CSU when compared with HCs, 31 (79.48%) were confirmed by qPCR corresponding to genes involved in epidermal homeostasis and dermal repair. From the analysis comparing LS-CSU with NLS-CSU, a selection of 142 genes was studied with qPCR, and 103 (72.53%) were confirmed. Differentially expressed genes in the phenomenon of wheal development are involved in a variety of biological functions as, epidermal differentiation, intracellular signal function, transcriptional factors cell cycle differentiation, inflammation, or coagulation. Differentially expressed genes that uniformly increase or decrease along the skin worsening until the wheal appearance is shown. CONCLUSION: The skin of CSU patients with a severely active disease shows an overall immunological skin involvement showing a peculiar gene profile.

Vulvar Basal Cell Carcinoma: Four Case Reports With Immunohistochemical Study.

Basal cell carcinomas (BCC) are the most frequent tumours in humans and normally appear in photoexposed areas of the skin. It is widely accepted that BCCs originate at follicular stem cells and consequently are very rare in nonhairy areas. Here, we report 4 cases of vulvar BCC, 3 of which were located in a vulvar semimucous area, a nonphotoexposed area, and a nonhairy area. We have determined the CK7 and CK19 profile of all cases; both are markers of simple epithelium with glandular differentiation. Interestingly, all cases were positively stained for CK7 and CK19. Considering that the vulvar region is rich in sebaceous and apocrine units, we hypothesise a glandular origin of BCCs situated in the vulvar region.