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Over the past few decades, a number of scoring instruments have been developed to assess the severity and activity of autoimmune bullous diseases (AIBDs) (Daneshpazhooh et al., 2019; Nili et al., 2020; Nili et al., 2021; Nili et al., 2022). The Pemphigus Disease Area Index (PDAI), developed by the International Pemphigus Definitions Group, is an easy‐to‐use, quick, and reliable method for determining pemphigus severity. As a reliable and effective tool in clinical trials, PDAI may also have some limitations and might require some revisions to be used on a daily basis. Here, we propose some recommendations to improve the use of PDAI in the clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: This study determines the healing time of lesions on different locations and the contributing factors to the healing time in patients with pemphigus. Methods: In this prospective study, newly diagnosed patients with mucosal lesions were included. A dermatologist evaluated the lesions, disease status, side effects and assigned the PDAI. Follow‐up visits were conducted monthly until the patient reached complete remission and every three months thereafter. A Tzanck smear was performed on lesions clinically suspected to be herpetic in origin. Results: Sixty patients enrolled in the study with a mean age of 45.9 ± 11.7 years. The buccal lesions took the longest to resolve (73[33.5–105.5] days). However, the posterior pharynx lesions showed the shortest healing time (20[13.0–25.5] days). The likelihood of improvement in buccal and soft palate lesions decreased by 5% and 3% with each additional year of age, respectively. Also, the resolution duration of soft palate lesions was significantly shorter in female patients than males (median of 24.0 days vs. 38.5 days). In contrast, lower gingival lesions resolve significantly faster in male patients by a median of 9 days. Herpes simplex virus infection increases the healing time of lesions by 26 days (median of 55 days vs. 29 days, hazard ratio 2.62, 95% CI: 1.04–5.92). Conclusions: Buccal and lower gingival lesions are more recalcitrant to treatment, while posterior pharynx lesions heal most rapidly. Furthermore, older age was also associated with a lower rate of lesion improvement. [ABSTRACT FROM AUTHOR]

Actinic keratosis (AK) is a pre-cancerous skin lesion, associated with development of squamous cell carcinoma. Current treatment options are limited. To compare the efficacy and safety of topical 5-fluorouracil cream (5-FU) and potassium hydroxide 5% (KOH) in the treatment of AK. Eighteen patients with AK applied KOH solution or 5-FU on each side of their scalp/face, randomly. The efficacy and safety of these treatments were compared. Thirteen (118 lesions) and ten (83 lesions) patients were successfully followed for one and three months, respectively. After one month, KOH showed a better clinical response (81% vs. 58%; p-value = 0.007) and dermoscopic response (KOH, 65% vs. 5-FU, 46%; p-value = 0.04); while no differences were noted after three months (clinical response, 83% vs.70%, p-value = 0.1; dermoscopic response, 76% vs. 59%, p-value = 0.1). No significant differences in the recurrence rate of the lesion between the two groups were noted at the end of the third month (p-value = 0.5). Regarding the safety of the treatments, the risk of developing erythema, scaling, sand swelling was higher in 5-FU group (p-value < 0.0001, for all), while more patients in KOH group had erosion and ulcer (p-value < 0.001 for both). KOH was up to 96% less expensive than 5-FU. Low number of patients and short-term follow-up limited the analysis. KOH solution offers a faster and less expensive resolution of AK lesions than does 5-FU. IRCT20180909040978N1 [ABSTRACT FROM AUTHOR]

Frontal fibrosing alopecia (FFA) is a scarring alopecia with no promising treatment. To evaluate the additive efficacy of oral isotretinoin to topical treatments. Between November 2017 and August 2018, FFA patients were randomly assigned to receive either isotretinoin (20 mg/d) plus topical treatments (clobetasol 0.05% and tacrolimus 0.1%) or monotherapy with topical treatments. Treatments' efficacy was evaluated through Frontal Fibrosing Alopecia Severity Index (FFASI) after two and 6 months. From 38 participants, 28 patients completed the study. Facial papules improved after 6 months (p value <.001) in the isotretinoin group. Moreover, frontotemporal hairline (p values for frontal <.001; R lateral: 0.03; L Lateral: 0.02), total scalp margins, total additional features' scores, and total combined (p value <.001 for all) improved more in the isotretinoin group than in the control group. Frontal band improved in the treatment group (p value:.02). Frontal margin (p value:.01), R lateral (p value:.01), total scalp (p value <.01), and combined total scores (p value:.01) worsened in the control group. Isotretinoin-related side-effects included lip dryness, telogen effluvium, and malaise. Small sample size and lost to follow-up. Isotretinoin combined with topical treatments is more effective than monotherapy with clobetasol and tacrolimus for FFA. (IRCT.ir) IRCT2017091736173N1. [ABSTRACT FROM AUTHOR]

The patient did not develop any new lesions during the next 3 months; she was in complete remission on minimal therapy 5 months after biosimilar RTX injection (prednisolone 7.5 mg/day). In addition to the development or reactivation of infections, rare adverse events such as neutropenia and pemphigus worsening after RTX therapy have been reported.3,5,6 There was a probable association with AGEP following RTX in both cases (based on Naranjo scale scores of 7 for both). Dear Editor, Acute generalized exanthematous pustulosis (AGEP) is a rare drug reaction characterized by widespread, sterile pustular lesions throughout the skin.1 AGEP following biologic drugs such as etanercept and tocilizumab have been reported.2 The Food and Drug Administration (FDA) recently approved rituximab (RTX) as a treatment for adult patients with moderate to severe pemphigus vulgaris (PV).3 Here, we report two patients with pemphigus developing AGEP following biosimilar RTX administration. [Extracted from the article]

Background: Port Wine Stain (PWS) is a congenital capillary malformation. Although multiple treatments are required, the gold standard treatment for PWS is Pulsed Dye Laser (PDL). Given its anti‐angiogenic effects, sirolimus can be considered as an adjuvant to PDL in PWS. Aim: To evaluate the efficacy and safety of topical sirolimus (Rapamycin) 0.2% cream as adjuvant therapy for PDL for PWS. Methods: In this randomized double‐blind placebo‐controlled trial, 15 patients with PWS were enrolled. Each lesion was divided into upper and lower parts, and each part was assigned randomly to receive PDL (4 sessions, 2 months apart) plus sirolimus vs PDL and placebo. The response was evaluated using colorimetry, investigator global assessment (IGA), and patient global assessment (PGA) every two months for eight continuous months. Results: According to the colorimetric analysis, medial and lateral sides of the treatment and placebo parts did not differ significantly (both P‐value >.05). However, according to PGA and IGA, there was a significant difference in favor of sirolimus (P‐values =.041 and.039, respectively). Itching and dryness (86.7%), contact dermatitis (20%) were the most common adverse effects in the sirolimus group, while none of them were observed in placebo. Conclusion: Although the improvement was significant subjectively, topical sirolimus 0.2% as an adjuvant to PDL does not appear to improve PWS erythema using calorimetric assessment. [ABSTRACT FROM AUTHOR]

The median duration of remission in treatment-naive patients was 33.5 months, while it was 21.0 months in those who received RTX as second-line treatment ( I P i -value = 0.27). In a series of five moderate PV patients treated with RTX monotherapy, two experienced complete remission, and three had several relapses after a mean follow-up of 16 months. Dear Editor, Rituximab (RTX), an anti-CD20+ agent, has been approved for the treatment of moderate-to-severe I Pemphigus vulgaris i ([1],[2]). From January 2007 to June 2020, by screening 940 medical records of pemphigus patients with a history of RTX administration, we found 15 patients (11 women) with a history of at least one cycle of RTX monotherapy. [Extracted from the article]

Pemphigus is a rare group of autoimmune diseases, which its exact molecular pathogenesis and therapeutic biomarkers remained unknown. In this regard the expressions of eight immune‐related genes was evalualted in pemphigus patients. Forty‐six pemphigus patients, either new case or on minimal therapy, were recruited. The expressions of IL22, IL9, IL21, EBI3, TNFSF13B, FCGR3A, CTLA4, and PDCD1 genes were analyzed at baseline, compared with 32 healthy controls, and their changes were monitored 3 months after rituximab (RTX) therapy through Reverse Transcriptase Real‐time PCR (RT‐Real‐time PCR). Except of IL21, which was similar in both groups, expressions of other genes were significantly lower in patients compared with the controls (P‐value <.05). PDCD1, EBI3, IL21, and IL22 genes were significantly overexpressed three months following RTX administration (P‐value <.05). Higher prednisolone dosage and PDAI‐score were positively correlated with CTLA4 and FCGR3A expressions after 3 months, respectively (P‐value =.019 and.048, respectively). Anti‐desmoglein 1 (Dsg 1) titer and its positivity at baseline were associated with TNFSF13B expression, FCGR3A expressions, and the PDAI‐score. Our results suggest the possible involvement of some gene expressions in pemphigus immunopathogenesis, which could be affected by RTX therapy and also might be used as prognostic biomarkers. [ABSTRACT FROM AUTHOR]

Although chimeric antigen receptor (CAR) T cell therapies have demonstrated promising clinical outcomes, durable remissions remain limited. To extend the efficacy of CAR T cells, we develop a CAR enhancer (CAR-E), comprising a CAR T cell antigen fused to an immunomodulatory molecule. Here we demonstrate this strategy using B cell maturation antigen (BCMA) CAR T cells for the treatment of multiple myeloma, with a CAR-E consisting of the BCMA fused to a low-affinity interleukin 2 (IL-2). This selectively induces IL-2 signaling in CAR T cells upon antigen-CAR binding, enhancing T cell activation and antitumor activity while reducing IL-2-associated toxicities. We show that the BCMA CAR-E selectively binds CAR T cells and increases CAR T cell proliferation, clearance of tumor cells and development of memory CAR T cells. The memory cells retain the ability to re-expand upon restimulation, effectively controlling tumor growth upon rechallenge. Mechanistic studies reveal the involvement of both CAR and IL-2 receptor endodomains in the CAR-E mechanism of action. The CAR-E approach avoids the need for specific engineering and enables CAR T cell therapy with lower cell doses., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)