Pemphigus Disease and Area Index: Unmet needs in the real-world management of pemphigus.

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.

Factors associated with the healing time of pemphigus vulgaris oral lesions: A prospective study.

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.

Investigating expression pattern of eight immune-related genes in pemphigus patients compared with the healthy controls and after rituximab therapy: Potential roles of CTLA4 and FCGR3A genes expression in outcomes of rituximab therapy.

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.

Exacerbation of Autoimmune Bullous Diseases After Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination: Is There Any Association?

Background and Aim: There have been concerns regarding the potential exacerbation of autoimmune bullous diseases (AIBDs) following vaccination against COVID-19 during the pandemic. In the current study, vaccine safety was evaluated in patients with AIBDs. Methods: In this study, patients with AIBDs were contacted via face-to-face visits or phone calls. Patient demographics, vaccine-related information, pre- and post-vaccine disease status, and complications were recorded. The exacerbation was considered either relapse in the remission/controlled phase of the disease or disease worsening in the active phase. The univariate and multivariate logistic regression tests were employed to determine the potential risk factors of disease exacerbation. Results: Of the patients contacted, 446 (74.3%) reported receiving at least one dose of vaccine injection (54.7% female). Post-vaccine exacerbation occurred in 66 (14.8%) patients. Besides, there were 5 (1.1%) patients with AIBD diagnosis after vaccination. According to the analysis, for every three patients who received vaccines during the active phase of the disease one experienced disease exacerbation. The rate of disease exacerbation increased by three percent with every passing month from the last rituximab infusion. Active disease in the past year was another risk factor with a number needed to harm of 10. Conclusion: Risk of AIBD exacerbation after the COVID-19 vaccine is not high enough to prevent vaccination. This unwanted side effect, can be reduced if the disease is controlled at the time of vaccination.

Comparing efficacy and safety of potassium hydroxide 5% solution with 5-fluorouracil cream in patients with actinic keratoses: a randomized controlled trial.

BACKGROUND: Actinic keratosis (AK) is a pre-cancerous skin lesion, associated with development of squamous cell carcinoma. Current treatment options are limited. OBJECTIVES: To compare the efficacy and safety of topical 5-fluorouracil cream (5-FU) and potassium hydroxide 5% (KOH) in the treatment of AK. METHODS: 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. RESULTS: 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. LIMITATIONS: Low number of patients and short-term follow-up limited the analysis. CONCLUSION: KOH solution offers a faster and less expensive resolution of AK lesions than does 5-FU. CLINICAL TRIAL CODE (IRCT.IR): IRCT20180909040978N1.

Oral isotretinoin combined with topical clobetasol 0.05% and tacrolimus 0.1% for the treatment of frontal fibrosing alopecia: a randomized controlled trial.

BACKGROUND: Frontal fibrosing alopecia (FFA) is a scarring alopecia with no promising treatment. OBJECTIVE: To evaluate the additive efficacy of oral isotretinoin to topical treatments. METHODS: 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. RESULTS: 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. LIMITATIONS: Small sample size and lost to follow-up. CONCLUSION: Isotretinoin combined with topical treatments is more effective than monotherapy with clobetasol and tacrolimus for FFA. CLINICAL TRIAL CODE: (IRCT.ir) IRCT2017091736173N1.

Current status and prospects for the diagnosis of pemphigus vulgaris.

Introduction: Pemphigus vulgaris (PV) is an intraepidermal autoimmune bullous disease (AIBD) characterized by autoantibodies against desmosomal adhesion proteins, most commonly desmoglein (Dsg)3, leading to the suprabasal cleft formation and acantholysis.Areas covered: Direct immunofluorescence (DIF) and indirect immunofluorescence (IIF) studies display the intercellular deposition of IgG/C3 throughout the epidermis and presence of circulating autoantibodies respectively, as a net-like pattern. However, the target antigen remains unknown using immunofluorescence techniques. Thanks to the development of Dsg ELISA, using recombinant technology, circulating antibodies against Dsg1 and 3 could be detected sensitively. It is possible to differentiate PV from pemphigus foliaceus (PF) using this assay. BIOCHIP mosaic and multivariant ELISA are two novel serologic methods with the added value of the ability to screen several AIBDs simultaneously.Non-Dsg1/3 antigens are also involved in the pathogenesis of PV and investigated more deeply thanks to the protein microarrays technique. Additionally, patients with high values of anti-Dsg1/3 may be lesion-free, suggesting the presence of nonpathogenic autoantibodies.Expert opinion: Newer diagnostic methods to replace traditional techniques should possess high sensitivity and specificity and be widely available, noninvasive, and relatively cheap. The newly developed methods need to be further evaluated before being recommended for routine use.

Evaluating the efficacy and safety of topical sirolimus 0.2% cream as adjuvant therapy with pulsed dye laser for the treatment of port wine stain: A randomized, double-blind, placebo-controlled trial.

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.