Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas.

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Experience With Bexarotene to Treat Cutaneous T-Cell Lymphomas: A Study of the Spanish Working Group of Cutaneous Lymphomas. / [Artículo traducido] Experiencia con bexaroteno en linfoma cutáneo de células T: un estudio del Grupo Español de Linfomas Cutáneos (GELC).

BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience. / [Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital.

COVID-19 is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2). Vesicular skin rashes have been reported as associated with COVID-19, but there is little information about this cutaneous manifestation. We designed a prospective observational study of patients diagnosed with COVID-19 who had vesicular lesions. Clinical characterization of skin findings was conducted by dermatologists. When possible, histological analysis and detection of SARS-CoV-2 in the content of the vesicles was performed. In total, 24 patients were included. A disseminated pattern was found in 18 patients (75%), and a localized pattern was found in 6 (25%). Median duration of the skin rash was 10 days. Of the 24 patients, 19 (79.2%) developed the skin rash after the onset of COVID-19 symptoms. Histological examination in two patients was consistent with viral infection, SARS-CoV-2 was not detected in four patients. This single-centre study shows the clinical characteristics of vesicular skin rashes in patients with COVID-19.

Split-face study comparing conventional MAL photodynamic therapy in multiple actinic keratosis with complete time vs. half-time red light LED conventional illumination.

BACKGROUND: Conventional photodynamic therapy (PDT) with methylaminolevulinic acid (MAL) and daylight PDT have demonstrated similar efficacy in the treatment of actinic keratosis (AK). The reason for the use of daylight is to reduce pain during illumination but daylight has the limitation of the weather conditions. The difference in the doses of red light applied between these two methods suggests that an intermediate dose with red light conventional illumination could be effective in PDT of AK. OBJECTIVE: To compare the efficiency of conventional MAL-PDT with half-time conventional red light illumination in patients with multiple AK. MATERIAL AND METHODS: Adult patients with more than five symmetrically distributed AK were selected. After randomization, one area was treated with conventional PDT (Aktilite® , 630 nm, 37 J/cm2 , 8 min), while the contralateral was illuminated half time (Aktilite® , 630 nm, 37 J/cm2 , 4 min). Patients evaluated pain in each different side. Patients were evaluated at baseline, 3 and 6 months after PDT treatment by a blinded dermatologist. A questionnaire to be done at home 24 h after completing treatment was deliver to the patients to evaluate any side-effects. RESULTS: A total of 774 lesions were treated, 385 with conventional PDT and 389 with half-time PDT (P > 0.05). Conventional PDT was 85% of complete response of AK (327/385) at 3 months, and half-time PDT was 82% (319/389). At 6 months, conventional PDT was 70% (268/385) of complete response and half-time PDT was 65% (252/389). Pain during illumination was significantly lower in the VAS with the half-time protocol with a mean of 5.59 (SD 1.48) vs. 6.41 (SD 1.66) in conventional PDT. No difference in adverse effects was found between protocols. CONCLUSION: Conventional PDT with half-time illumination in multiple actinic keratosis is as effective as complete time illumination and decreased pain significantly.

Treatment of adult diffuse pityriasis lichenoides chronica with narrowband ultraviolet B: experience and literature review.

Pityriasis lichenoides chronica (PLC) is an infrequent dermatosis of unknown aetiology, wholse evolution and response to treatment differs between children and adults. When PLC is recalcitrant or unresponsive to topical treatment, phototherapy is one of the main treatments used. We carried out a prospective study of adult diffuse PLC treated with narrowband ultraviolet B (NB-UVB). We treated eight patients whose disease showed no response to topical therapy, and obtained a complete response rate of 88% in a mean of 23 sessions (cumulative dose 16.99 J/cm2 ). However, the relapse rate was 43% in the first 6 months. Our results are similar to those of other published studies but there is much variability between them in the doses applied and the number of sessions needed. Further studies are necessary to devise a protocol for NB-UVB treatment of PLC.

Fluorescence diagnosis and photodynamic therapy for Bowen's disease treatment.

INTRODUCTION: It has already been demonstrated the high efficacy of photodynamic therapy (PDT) for Bowen's disease (BD) treatment. Fluorescence diagnosis consists on registration of the fluorescence emitted by tissue after application of a photosensitizer, indicating presence of tumoral cells. It has been described as a useful tool for actinic keratosis. Different results have been published about fluorescence diagnosis for basal cell carcinomas. Very few reports about the role of fluorescence diagnosis for this entity exist and this is the first one which correlates the fluorescence image after PDT with the histopathological response. OBJECTIVES: To assess the role of fluorescence diagnosis during BD follow-up. METHODS: We carried out an observational, retrospective and descriptive study. A total of 29 BD biopsy proven lesions were included. All the lesions had been treated with the standard protocol (Topical methyl- aminolaevulinic acid under occlusion for 3 hours and followed by illumination with red-light (630 nm, 38 J/cm(2), 7.5 minutes. Two sessions one week apart). Clinical and fluorescence photographs were taken before treatment and one month after the 2(nd) one. At that moment a post-treatment biopsy was performed. Clinical response was classified as partial, complete or no response. Fluorescence response was classified as negative, intermediate or intense. The follow-up period and the adverse events observed including pain were also collected. RESULTS: We found statistical association between fluorescence and the clinical and histopathological evaluations performed after treatment. Fluorescence diagnosis obtained a 100% sensitivity (higher than clinical evaluation alone) and a specificity of 85.7% (CI: 70.8-100). CONCLUSIONS: Fluorescence diagnosis seems a valid diagnostic tool, useful during the follow up of Bowen disease lesions with the advantage of avoiding unnecessary post-treatment biopsies.

Rituximab in the treatment of primary cutaneous B-cell lymphoma: a review.

Rituximab is a chimeric mouse-human antibody that targets the CD20 antigen, which is found in both normal and neoplastic B cells. In recent years, it has been increasingly used to treat cutaneous B-cell lymphoma and is now considered an alternative to classic treatment (radiotherapy and surgery) of 2 types of indolent lymphoma, namely, primary cutaneous follicle center lymphoma and primary cutaneous marginal zone B-cell lymphoma. Rituximab is also administered as an alternative to polychemotherapy in the treatment of primary cutaneous large B-cell lymphoma, leg type. Its use as an alternative drug led to it being administered intralesionally, with beneficial effects. In the present article, we review the literature published on the use of rituximab to treat primary cutaneous B-cell lymphoma.

Spontaneous regression of primary diffuse large B-cell lymphoma, leg type.

Primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL LT) accounts for approximately 20% of all primary cutaneous B-cell lymphomas and tends to present as infiltrated nodules, tumors, and plaques on the legs in the elderly. Unlike other primary cutaneous large B-cell lymphomas, it has a poor prognosis and tends to require treatment with systemic chemotherapy. We present the case of an 82-year-old patient with a 1-year history of nodules and plaques on her right leg. Biopsy led to a diagnosis of PCLBCL LT and the lesions resolved without treatment within 1 month of the first visit. This is an atypical course of PCLBCL LT and we believe that it is the first such case to be reported in the literature.

Photodynamic therapy in mycosis fungoides.

Photodynamic therapy involves the topical application of a photosensitizer to a lesion, which is then subsequently exposed to a light source. It is mainly used in the nonsurgical treatment of nonmelanoma skin cancer, in which it achieves good response and an excellent cosmetic result. In the last 10 years, photodynamic therapy has also been used with some success in the treatment of plaque-stage mycosis fungoides and has emerged as an alternative to skin-directed therapies. Its main advantages are the good response to treatment, lack of toxicity, and excellent cosmetic results. This article reviews the literature and the practical application of photodynamic therapy in mycosis fungoides.

Intralesional rituximab in the treatment of indolent primary cutaneous B-cell lymphomas: an epidemiological observational multicentre study. The Spanish Working Group on Cutaneous Lymphoma.

BACKGROUND: Intravenous rituximab is a safe and effective option for the treatment of systemic non-Hodgkin B-cell lymphoma. The effectiveness of intralesional rituximab (ILR) in primary cutaneous B-cell lymphomas (PCBL) has been described in a small number of patients. OBJECTIVES: To evaluate the effectiveness, tolerance and adverse effects of ILR in patients with follicle centre (FCL) and marginal zone (MZL) PCBL. METHODS: This was an epidemiological observational multicentre study of patients with PCBL treated with ILR. RESULTS: Seventeen patients with MZL and 18 with FCL PCBL were included. The median number of lesions treated was two per patient. The treatment regimen used in 74% of the patients was a course of three injections in a single week at 1-month intervals. The dose per lesion and day of treatment was 10 mg in 71% of the patients. The median cumulative dose of rituximab per lesion was 60 mg (range 13-270) and per patient was 150 mg (range 20-360 mg). Complete response (CR) and partial response were achieved in 71% and 23% of patients, respectively. The median time to CR in patients who received 10 mg of ILR per lesion was 8 weeks. Similar response rates were observed in MZL and FCL. Median disease-free survival was 114·1 weeks. No parameters that significantly predicted CR were identified. Adverse reactions were recorded in 19 patients; the most frequent was localized pain at the injection site. Median follow-up was 21 months. CONCLUSIONS: Intralesional rituximab is a well-tolerated and effective treatment for FCL and MZL PCBL. It should be considered a useful alternative in patients with recurrent lesions and in which the sequelae of radiotherapy or surgery would be significant.

Effectiveness of photodynamic therapy in Bowen's disease: an observational and descriptive study in 51 lesions.

INTRODUCTION: Bowen disease (BD) or squamous cell carcinoma (SCC) in situ affects both skin and mucous membranes and has the potential to progress to invasive SCC. Photodynamic therapy (PDT) has been approved recently for the treatment of BD. Some studies have demonstrated its efficacy and good cosmetic outcome. OBJECTIVE: To assess the efficacy of PDT in the treatment of BD. PATIENTS AND METHODS: We carried out an observational, retrospective and descriptive study. A total of 47 patients with 51 lesions of BD were included. All the lesions were confirmed with previous cutaneous biopsy. All patients were treated with the standard protocol. Topical methyl-aminolaevulinic acid was occluded during 3 h and followed by illumination with red-light (630 nm, 38 J/cm2, 7.5 min). Clinical and fluorescence photographs images were taken before each session. All patients received two sessions one week apart. Clinical response was classified in partial or complete response. Fluorescence response was classified in negative, intermediate or intense. The follow-up period and the adverse events observed including pain were also collected. RESULTS: A total of 20 men and 27 women with a mean age of 75.57 years old were treated with PDT. Lesions were most frequently located in the lower limbs. Globally, 76.09% of the lesions achieved complete response after 2 sessions with a medium follow-up of 16.61 months. Fluorescence of the lesions disappeared when clinical response was achieved, but not always. The most common adverse effect was an immediate burning sensation. All lesions showed an excellent cosmetic result. CONCLUSION: Photodynamic therapy is an effective treatment for BD in terms of both clinical remission and cosmetic results, with good tolerance and minimal adverse effects.

[Lymphomatoid papulosis: clinical and pathological findings in 18 patients]. / Papulosis linfomatoide: hallazgos clínico-patológicos en 18 pacientes.

BACKGROUND: Lymphomatoid papulosis (LyP) is a CD30(+) lymphoproliferative skin disease that has been described in association with Hodgkin lymphoma. It has also been reported to progress to mycosis fungoides or cutaneous anaplastic large-cell lymphoma. OBJECTIVE: To study the clinical and histologic features of LyP and response to treatment in a patient series. MATERIALS AND METHODS: For this retrospective, descriptive, observational study of patients with histologically confirmed LyP and sufficient follow-up data on record, we extracted histologic findings on skin biopsy, clinical presentation, clinical course, and response to treatments. RESULTS: Eighteen patients (10 male, 8 female) were identified. Most biopsies (14/18, 78%) showed a wedge-shaped lymphocytic infiltrate with CD30(+), CD3(+), and CD56(-) cells. A type A histologic pattern was present in the biopsies of 83% of the patients. The most common presentation (83%) consisted of papules on the trunk; for 62% LyP resolved after a single episode. Twelve percent of the patients developed mycosis fungoides (mean follow-up, 7 years); no other associations were noted. DISCUSSION: Although few series of patients with LyP have been published in recent years, the findings reported generally coincide with our observations. CONCLUSION: LyP is typically a CD30(+) lymphoproliferative disorder that usually runs a benign course and responds well to treatment.