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.

Human monkeypox virus in a tertiary hospital in Madrid, Spain: An observational study of the clinical and epidemiological characteristics of 53 cases.

A new outbreak of monkeypox virus (MPXV) infection, a zoonotic infection endemic in Central and West Africa, is spreading throughout the world with new epidemiology and clinical features. Our aim was to characterize patients presenting to Dermatology emergency room with a MPXV infection between 15 May and 30 June 2022 in a tertiary hospital in Madrid, Spain. We collected 53 patients and describe their clinical, demographic and epidemiological characteristics and followed their evolution. Most of the patients were men who had sex with men with high-risk sexual practices and no recent travels abroad. Most of them (91%) had had a sexually transmitted infection before. All patients had typical skin lesions consisting of vesicular-pustular rash with central umbilication which was localized or disseminated. The most frequent extracutaneous symptoms were fever, painful regional lymphadenopathy and asthenia. Proctitis was present in more than one third of patients. All patients were diagnosed by real time polymerase chain reaction of samples obtained from skin lesions. Pharyngeal and/or rectal exudates demonstrated MPXV in 74% of patients. The current worldwide outbreak of MPXV infections shows epidemiological and clinical differences from previous ones. Clinicians should be aware of these characteristics to correctly diagnose this emerging disease.

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.

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.

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.

Defining dipeptidyl peptidase-4 inhibitors-related bullous pemphigoid: A single-centre retrospective study.

BACKGROUND: Many studies have corroborated the association of dipeptidyl peptidase-4 inhibitors (DPP4i) use with bullous pemphigoid (BP). It has been speculated that this drug-induced variant presents with a different clinical spectrum than conventional BP. OBJECTIVE: To determine the prevalence of DPP4i-induced cases of BP and to evaluate whether gliptin-related BP has specific clinicopathological and immunological features. METHODS: We conducted a retrospective, observational study of BP cases attended at our centre between January 2000 and June 2020. Epidemiological, clinical, histopathological and laboratory data were collected. RESULTS: A total of 257 cases of BP were collected; 51 (24.3%) were on treatment with DPP4i. When analysing DPP4i-induced BP cases, generalized BP was the predominant pattern and scalp/mucosal involvement was found in 13 patients. Gliptin-related BP cases were associated to a decrease in the eosinophilic infiltrate (p = 0.000) and both the detection rate and concentration of anti-BP180 IgG were lower (p = 0.004, p = 0.001, respectively) than non-DPP4i cases. LIMITATIONS: Retrospective, single-centre study. CONCLUSION: Our large DPP4i-induced BP case series has highlighted that DPP4i-induced BP is characterized by generalized lesions and scalp involvement. Lower titres of anti-BP180 antibodies and a decrease in eosinophils infiltrating into the skin may be distinct features of DPP4i-related BP.