Safety of biologic therapy in combination with methotrexate in moderate to severe psoriasis: a cohort study from the BIOBADADERM registry.

BACKGROUND: Safety is an important consideration in decisions on treatment for patients with moderate-to-severe psoriasis and the study of drug safety is the main purpose of the BIOBADADERM registry. The combination of a biologic agent and a conventional systemic drug [generally methotrexate (MTX)] is a common treatment in clinical practice. However, there is a paucity of evidence from real-world practice on the safety of such combination regimens in the treatment of psoriasis. OBJECTIVES: The primary objective of this study was to ascertain whether the use of regimens combining biologic drugs with MTX in the management of moderate-to-severe psoriasis increases the risk of adverse events (AEs) or serious AEs (SAEs). We compared monotherapy using tumour necrosis factor (TNF), interleukin (IL)-17 and IL-23 inhibitors with the use of the same drugs in combination with MTX. METHODS: Using data from the BIOBADADERM registry, we compared biologic monotherapies with therapies that were combined with MTX. We estimated adjusted incidence rate ratios (aIRR) using a random effects Poisson regression with 95% confidence intervals for all AEs, SAEs, infections and serious infections and other AEs by system organ class. RESULTS: We analysed data from 2829 patients and 5441 treatment cycles, a total of 12 853 patient-years. The combination of a biologic with MTX was not associated with statistically significant increases in overall risk of AEs or SAEs in any treatment group. No increase in the total number of infections or serious infections in patients receiving combined therapy was observed for any group. However, treatment with a TNF inhibitor combined with MTX was associated with an increase in the incidence of gastrointestinal AEs (aIRR 2.50, 95% CI 1.57-3.98; P < 0.002). CONCLUSIONS: The risk of AEs and SAEs was not significantly increased in patients with moderate-to-severe psoriasis receiving different classes of biologic drugs combined with MTX compared with those on biologic monotherapy.

A novel pathogenic variation of DOCK6 gene: the genotype-phenotype correlation in Adams-Oliver syndrome.

BACKGROUND: Adams-Oliver syndrome (AOS) (#614,219) is a multiple malformation disorder characterized by the presence of aplasia cutis congenita (ACC) and transverse terminal limb defects (TTLD). METHODS AND RESULTS: We describe a confirmed case of AOS with a novel pathogenic variation in Dedicator Of Cytokinesis 6 (DOCK6) gene, with neurological abnormalities, characterized by the presence of a multiple malformation entity with extensive cardiological and neurological abnormalities. CONCLUSIONS: In AOS, genotype-phenotype correlations have been described. DOCK6 mutations appear to be related with congenital cardiac and central nervous system malformations associated with intellectual disability, as illustrated in the present case.

Effectiveness of neoadjuvant intralesional methotrexate in cutaneous squamous cell carcinoma: A prospective cohorts study.

Intralesional methotrexate (il-MTX) has been used in cutaneous squamous cell carcinoma (cSCC) achieving important reductions in tumor size. However, there is a lack of controlled studies on this regard. The primary objective was to analyze the effect of il-MTX on tumor size in cSCC. As a secondary objective, we evaluated its impact on the surgical approach. We conducted a prospective cohorts study that included 200 patients with histologically confirmed cSCC. Patients in Group 1 (Cases) received neoadjuvant treatment with il-MTX prior to surgery. Patients in Group 2 (Controls) underwent scheduled surgery without prior neoadjuvant therapy. Clinical measurements of lesions were made at the time of inclusion in the study and before surgery. No intergroup statistical differences were found between the assessed variables. In Group 1, tumor size reduction occurred in 93% of the patients after il-MTX therapy. Tumor surface was reduced by 54%. Complex reconstructions were needed in 15% of these patients. In Group 2, tumor surface increased by 33.1% and complex reconstructions were needed in 40% of patients. Intergroup differences were statistically significant (p < 0.001). Neoadjuvant Il-MTX therapy achieves very important tumor size reduction and significantly simplifies surgical treatment.

The risk of hepatic adverse events of systemic medications for psoriasis: a prospective cohort study using the BIOBADADERM registry.

BACKGROUND: Limited information is available regarding the risk of incident liver disease in patients with psoriasis receiving systemic therapies. OBJECTIVES: To describe the liver safety findings of conventional and modern systemic therapies for moderate-to-severe psoriasis, and to compare the relative incidence rates of hepatic adverse events (AEs) for each drug. METHODS: All the patients on the BIOBADADERM registry were included. Crude and adjusted incidence rate ratios (cIRR and aIRR, respectively) of hepatic AEs, using anti-TNF drugs as reference, were determined. Outcomes of interest were hypertransaminasemia, nonalcoholic fatty liver disease (NADFLD) and a group of other, less represented, hepatic AEs. RESULTS: Our study included 3,171 patients exposed to systemic drugs (6279 treatment cycles). Incident hypertransaminasemia was the most frequent hepatic AE (incidence rate of 21 per 1000 patients-years [CI 95% 18-23]), followed by NAFLD (8 cases per 1000 patients-years [95% CI 6-10]). Methotrexate (aIRR 3.06 [2.31-4.4]; p = 0.000) and cyclosporine (aIRR 2.37 [1.05-5.35]; p = .0378) were associated with an increased risk for hypertransaminasemia when compared to anti-TNF-α agents. No differences were observed between different groups of biologics. Conventional therapies were not associated with new incident NAFLD. CONCLUSIONS: Comparative information of the incidence of hepatic AEs could facilitate drug selection in moderate-to-severe psoriasis.

Tumor-like herpes simplex infection in an HIV patient

Abstract A 56-year-old male, HIV-positive, presented with a 3-day history of multiple indurated erythematous nodules with superficial and well-defined erosions on his right gluteus. Skin biopsy showed ballooning-necrotic keratinocytes and cultures were positive for herpes simplex 2. Genital herpes simplex infection recurrences may not be restricted to the anterior part of the genitalia and clinical presentation in the lumbar area or gluteus must be differentiated from varicella-zoster virus infection. Tumor-like presentation is a very rare manifestation of HSV cutaneous infection. It is important to take this morphological variant into consideration not to delay the diagnosis of a viral infection, especially in an immunosuppressed patient.

Dermoscopic Predictors of Tumor Thickness in Cutaneous Melanoma: A Retrospective Analysis of 245 Melanomas.

INTRODUCTION: The literature regarding the association of dermoscopic structures with Breslow thickness in melanoma is scarce, limited to small case series, and mostly outdated. OBJECTIVE: This study determined the dermoscopic patterns, colors and structures that are associated with melanoma in situ, thin melanomas (<0.8 mm) and thick melanomas potentially requiring sentinel lymph node biopsy according to current guidelines (≥0.8 mm). METHODS: A retrospective evaluation of 245 dermoscopic images of primary cutaneous melanoma located on the trunk or limbs was performed by consensus of 2 dermoscopists. RESULTS: Red-pink, blue-gray and white color, blue-white veil, shiny white streaks, irregular vessels, blue-black pigmentation, milky red areas, pseudolacunae, ulceration and rainbow pattern were associated with thickness ≥0.8 mm, whereas atypical pigmented network, regression and hypopigmented areas were significantly associated with early melanomas. LIMITATIONS: This is a retrospective study performed in a single institution. Melanomas of special sites were excluded from our evaluation. Dermoscopy is based on subjective evaluations that depend largely on the observers' experience. CONCLUSIONS: The identification of certain dermoscopic structures and colors might help in the discrimination between thin and thick melanomas.

Tumor-like herpes simplex infection in an HIV patient.

A 56-year-old male, HIV-positive, presented with a 3-day history of multiple indurated erythematous nodules with superficial and well-defined erosions on his right gluteus. Skin biopsy showed ballooning-necrotic keratinocytes and cultures were positive for herpes simplex 2. Genital herpes simplex infection recurrences may not be restricted to the anterior part of the genitalia and clinical presentation in the lumbar area or gluteus must be differentiated from varicella-zoster virus infection. Tumor-like presentation is a very rare manifestation of HSV cutaneous infection. It is important to take this morphological variant into consideration not to delay the diagnosis of a viral infection, especially in an immunosuppressed patient.

Mohs micrographic surgery in dermatofibrosarcoma protuberans: Rate and risk factors for recurrence in a prospective cohort study from the Spanish Registry of Mohs Surgery (REGESMOHS) and review of the literature.

Characterization of patients, surgery procedures and the risk factors for dermatofibrosarcoma protuberans (DFSP) recurrences is poorly defined. In this study, we aimed to describe the demographics, tumor characteristics and interventions of DFSP treated with Mohs micrographic surgery (MSS) to determine the rate and risk factors for recurrence. Data were collected from REGESMOHS, a nationwide prospective cohort study of patients treated with MMS in Spain. From July 2013 to February 2020, 163 patients with DFSP who underwent MMS were included. DFSP was mostly located on trunk and extremities. Recurrent tumors had deeper tumor invasion and required higher number of MMS stages. Paraffin MMS was the most frequently used technique. Overall recurrence rate was 0.97 cases/100 person-years (95% IC = 0.36-2.57). No differences were found in epidemiological, tumor, surgery characteristics or surgical technique (frozen or paraffin MMS [p = 0.6641]) in terms of recurrence. Median follow-up time was 28.6 months with 414 patient-years of follow-up. In conclusion, we found an overall low recurrence rate of DFSP treated with MMS. None of the studied risk factors, including MMS techniques, was associated with higher risk for recurrence.

Ectodermal dysplasia with congenital adermatoglyphia (Basan syndrome): Report of two cases presenting with extensive congenital milia.

Basan syndrome is a rare autosomal dominant genodermatosis, characterized by rapidly healing congenital acral bullae, congenital milia and adermatoglyphia (lack of finger and toeprints). This type of ectodermal dysplasia has been infrequently reported in the literature. A pathogenic mutation in the SMARCAD1 gene has been demonstrated to cause this rare disorder.

Histopathological findings in COVID-19-induced cutaneous lesions. Clinicopathological correlation of SARS-CoV-19 dermatologic patterns: review of the literature.

An increasing number of publications have brought attention to COVID-19-associated cutaneous lesions. Histopathological descriptions and clinical correlation of the histopathological findings of COVID-19 skin lesions are lacking. In this manuscript, we reviewed and described the histopathological characteristics of COVID-19 infection cutaneous patterns reported in the literature.

Histological findings after intralesional methotrexate treatment in cutaneous squamous cell carcinoma.

Intralesional methotrexate (il-MTX) has been reported as a useful therapy in keratoacanthoma (KA) and cutaneous squamous cell carcinoma (cSCC). However, the data available on the histological changes induced by this therapy are very scarce. We conducted a single center, prospective study that included 65 cases of cSCC treated with il-MTX before surgical treatment. Two histological studies were conducted in all patients: before intralesional treatment and after surgical removal. Lesions were assessed longitudinally both clinically and histologically. 60 patients (92.3%) responded to il-MTX treatment. There were no differences regarding aggressive histological features of the cSCC between responder and non-responder patients. All cases showed a chronic inflammatory infiltrate after il-MTX. Intratumoral necrosis areas were frequently observed. All cases showed local fibrosis with fine thickening of collagen bundles. Il-MTX induces a chronic lymphohistiocytic inflammatory reaction in both clinical responder and nonresponder patients. Tumor involution after il-MTX is followed by a fine fibrosis that explains the great cosmetic results and improves the accuracy of the follow-up.

Cutaneous infiltration by T-cell prolymphocytic leukemia in two adult patients. / Infiltración cutánea por leucemia prolinfocítica T en dos pacientes adultos.

BACKGROUND: T-cell prolymphocytic leukemia (T-PLL) is a T-cell lymphoproliferative disorder that frequently involves the skin. The objective was to describe two cases of T-PLL with cutaneous involvement and to present a review of the literature concerning the clinical characteristics, differential diagnosis and treatment of these patients. CASE REPORTS: 1) 79 year-old man, with a previous diagnosis of T-PLL based on a laboratory incidental finding. He had been treated with alemtuzumab, but it had to be interrupted due to recurrent infections. After interrupting the treatment, the patient developed a symmetrical rash on his extremities. The skin biopsy demonstrated TPLL infiltration. 2) 28 year-old man that presented with asthenia and lymphocytosis. He also showed a purpuric rash on his trunk and facial erythema. Histopathology of the skin and bone marrow confirmed the diagnosis of T-PLL with cutaneous involvement. CONCLUSIONS: T-cell prolymphocytic leukemia accounts for 2% of mature leukemias in adults. Skin involvement is reported in 20-50% of the patients. The characteristic features are facial involvement, purpuric lesions and symmetry of the rash, although there are atypical manifestations as well. Differential diagnosis includes other T-cell lymphoproliferative disorders with hematologic and skin involvement, such as Sézary syndrome. Patients with T-PLL may show cutaneous infiltration at the moment of debut or relapse of the disease. The skin is an accessible organ for taking samples to study and diagnose these patients.

INTRODUCCIÓN: La leucemia prolinfocítica T (LPL-T) es una neoplasia hematológica del grupo de síndromes linfoproliferativos T que con frecuencia produce infiltración cutánea. Se presentan dos casos de LPL-T con afectación cutánea y se revisa la literatura en cuanto a características clínicas, diagnóstico diferencial y tratamiento de estos pacientes. CASOS CLÍNICOS: 1) Varón de 79 años diagnosticado de LPL-T tras un hallazgo analítico incidental. Tras suspender el tratamiento con alemtuzumab por infecciones recurrentes, comenzó con lesiones cutáneas maculopapulosas eritematopurpúricas que afectaban la raíz de las extremidades. La biopsia cutánea confirmó la infiltración por su enfermedad de base. 2) Varón de 28 años que debutó con astenia y hallazgos analíticos de leucocitosis. Había comenzado además con lesiones purpúricas en el tronco y eritema malar bilateral. El estudio de médula ósea y la biopsia cutánea confirmaron el diagnóstico de LPL-T con infiltración cutánea. CONCLUSIONES: La LPL-T corresponde al 2% de las leucemias linfocíticas maduras en los adultos. Entre el 20% y el 50% de los pacientes presentan afectación cutánea, con predominio en la región facial, y son característicos el eritema, la púrpura y la simetría, aunque existen manifestaciones atípicas. El diagnóstico diferencial incluye otros síndromes linfoproliferativos T con afectación cutánea y en sangre periférica, entre los que destaca el síndrome de Sézary. Los pacientes con LPL-T pueden presentar afectación cutánea en el debut o en una recidiva de la enfermedad. La piel representa un órgano accesible para la toma de muestras y para el diagnóstico y el estudio de estos pacientes.

Dermoscopy of cutaneous melanoma metastases: A color-based pattern classification.

Dermoscopic studies about cutaneous metastases of malignant melanoma (CMMM) are few. Our objective was to analyze the dermoscopic features of CMMM and propose a new dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features. A retrospective evaluation of 150 dermoscopic images of CMMM taken from 40 patients was performed. One hundred CMMM images were individually evaluated by six dermatologists in order to classify them according to four dermoscopic patterns: (i) blue pattern; (ii) pink pattern; (iii) brown pattern; and (iv) mixed pattern. One hundred and fifty dermoscopic images including 50 CMMM and 100 benign lesions were evaluated by five dermatologists to calculate the accuracy of these patterns in the recognition of CMMM. An intra- and interobserver reproducibility agreement study between all different dermoscopic pattern classifications was performed. Seventy-five percent of our cases of CMMM showed a monochromatic pattern. Light brown pigmented halo, peripheral gray spots and polymorphic atypical vessels were the most significant focal dermoscopic structures. The reproducibility of the color-based dermoscopic pattern classification was superior to previous dermoscopic pattern classification. In summary, a dermoscopic pattern classification based on color pigmentation and some specific dermoscopic features may be useful in recognizing early cutaneous melanoma metastasis. Multicentric studies are recommended in order to lower the impact of interobserver variability.