Combination therapy for management of pemphigus patients with unexpected therapeutic response to rituximab: A report of five cases.

Key Clinical Message: The immunosuppressant agents should be considered earlier in the course of treatment with rituximab, possibly after the unfavorable response at first cycle of treatment, especially in male patients and those with high BMI. Abstract: Rituximab (RTX) has recently been proposed as an alternative first-line therapy for pemphigus patients. However, there are some rare reports of worsening of pemphigus following RTX therapy in the literature. This study aimed to evaluate the efficacy and safety of using a combination treatment of mycophenolate mofetil or dapsone and methotrexate in case of nonresponse, exacerbation or development of allergic reactions following rituximab therapy in pemphigus patients. In this case series, archive files of pemphigus patient in a tertiary care hospital from 2016 to 2021 who were treated with rituximab were reviewed and those with failure in treatment process including nonresponsiveness, exacerbation or development of allergic reactions to rituximab were identified and assessed. The study includes five patients out of 1245 RTX-treated patients, who did not respond to RTX (one patient) or experienced an exacerbation of disease (two patients) or development of allergic reactions (two patients). Male patients with high BMI (BMI > 25) whose response to rituximab was not good at first cycle and happened to receive rituximab later in the course of disease, had highest number of relapses and benefited the most from this combination immunosuppressive treatment as an alternative for repeating rituximab cycles. The lower risk of relapse and a better chance of remission might indicate the efficacy of adjuvant immunosuppressant therapy in patients with no-response, exacerbation, or allergic reaction to rituximab. These therapeutic effects were better observed in patients who received lower doses of rituximab which could suggest that the immunosuppressant agents should be considered earlier in the course of the disease, possibly after the first failed trial of rituximab therapy.

Oxidative stress and antioxidant markers in patients with alopecia areata: A comparative cross-sectional study.

Background Alopecia areata is a chronic inflammatory skin disease. Oxidative stress may contribute to the pathogenesis of this condition. Aim To evaluate the serum oxidative stress markers and antioxidant capacity in patients with alopecia areata. Methods This cross-sectional study was performed on 40 patients with alopecia areata and 40 healthy controls. The fasting blood sugar, C-reactive protein, lipid profile, and serum oxidative markers, including advanced glycation end products and advanced oxidation protein products, were measured in this study. Also, antioxidant enzymes, including paraoxonase-1, lecithin-cholesterol acyltransferase and serum ferric-reducing antioxidant power, were determined. Results The serum levels of advanced glycation end products and advanced oxidation protein products were significantly higher in patients with alopecia areata, compared to the controls (P < 0.001), whereas the levels of ferric-reducing antioxidant power, paraoxonase-1 and lecithin-cholesterol acyltransferase were significantly lower in patients with alopecia areata, compared to the controls (P < 0.001). The mean fasting blood sugar level was significantly higher in patients with alopecia areata, compared to the controls. The ferric reducing antioxidant power level was significantly associated with the percentage of hair loss (P = 0.01, r = 0.4) and the serum C-reactive protein level (P = 0.03, r = -0.3) in patients with alopecia areata. Limitations Since the current study had a cross-sectional design, no cause-effect relationship was established between alopecia areata and oxidative stress. The sample size of our study was also small. Conclusion Based on the present results, the oxidant-antioxidant enzymatic system is impaired in alopecia areata due to the increased oxidative products and decreased antioxidant activity.

Coexistence of Pemphigus Vulgaris and Lichen Planus following COVID-19 Vaccination.

SARS-CoV-2 vaccines were approved without long-term monitoring due to emergent situation and might have several side effects. Herein, we describe the first case with development of both LP and PV following COVID-19 vaccination. Immunological alteration due to COVID-19 vaccination and its potential role in triggering autoimmune disorders were also dealt with.

Clinical efficacy of mychophenolate mofetil in treating lichen planopilaris.

Lichen planopilaris (LPP) is a chronic inflammatory disorder of hair without a proven effective and safe treatment. To objectively assess the clinical efficacy of mycophenolate mofetil (MMF) in patients suffering from LPP, a retrospective cohort study was conducted on 52 patients who treated with MMF (2 g/day) at least for 6 months. LPP activity index (LPPAI) before and after treatment was calculated and compared. Most of the patients were female and belonged to the age group of 50-60 years. All of the disease activity indices were significantly improved after 6 months of therapy (p < 0.001). The majority of patients had LPPAI 4-6 and 0-2, before and after treatment, respectively. After 6 months of treatment, half of patients showed a disease activity decrease (LPPAI reduced >25% compared to the baseline value). Systemic MMF is an effective and relatively safe treatment modality for patients with LPP and could lead to significant reduction in disease activity regarding both subjective and objective indices.

Overestimation of subclinical atherosclerosis in psoriasis.

This study is one of a few that have been conducted to evaluate subclinical atherosclerosis in Iranian patients with psoriasis. Based on our findings, routine ultrasonography evaluation of all of patients with psoriasis does not seem to be reasonable or cost-effective.

Metabolic derangement in patients with vitiligo: a cross-sectional study.

Vitiligo is a pigmentary disorder resulting from progressive destruction of melanocytes in the skin. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including vitiligo. We aimed to evaluate lipid profile, leptin and C reactive protein (CRP) status among Iranian patients with vitiligo, compared with healthy controls and perused the relationship between abnormal values of these parameters with disease duration and physical characteristics of patients. 40 patients with vitiligo and 40 age-matched and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin and CRP values were recorded and compared. The mean values for nearly all study parameters (except for high-density lipoprotein) were significantly higher in patients with vitiligo, compared with healthy controls, irrespective of age and sex. We could not find any correlation between vitiligo and study parameters, regarding disease severity and extension of lesions; but in patients who have been suffering from vitiligo for more than 5 years, systolic blood pressure, diastolic blood pressure and CRP values were noted to be significantly higher (p<0.001, p=0.003 and p=0.03, respectively). In conclusion, screening of patients with vitiligo in regard to their lipid profile as well as blood pressure should be considered, especially in patients with longer disease duration or those who have other cardiovascular risk factors to prevent morbidity and mortality as a result of developing cardiovascular events.

Pemphigus patients with initial negative levels of anti-desmoglein: A subtype with different profile?

Pemphigus is a blistering autoimmune disease that is characterized by autoantibodies against desmogleins (Dsg), including anti-Dsg1 and anti-Dsg3. Despite the diagnosis of diseases, the anti-Dsg test by enzyme-linked immunosorbent assay (ELISA) is negative in a small group of pemphigus patients. The aim of this study was to evaluate the clinical course, clinical symptoms, and response to treatment in pemphigus patients with negative levels of anti-Dsg1 and anti-Dsg3. In this study, the data of pemphigus patients referred to Razi Hospital were retrospectively collected from the medical records from 2016 to 2020. Eight patients, whose initial anti-Dsg1/anti-Dsg3 was negative by the ELISA test, were enrolled and their clinical course, clinical signs, and response to treatment were evaluated. The mean age of the subjects (8 females) was 38.75 ± 12.09. The most common phenotype of the subjects was pemphigus vulgaris (PV) with mucosal involvement. Additionally, the common site of blister inception was mouth of the patients. The mean prednisolone dose received by the patients at the initiation was 32.5 ± 13.62 mg/day. According to Pemphigus disease area index (PDAI), six patients had mild severity, while two cases had moderate severity. Among the patients, six subjects received rituximab (RTX). Also, five patients experienced remission after 6.2 ± 5.21 months. PV is the most common phenotype of the disease and mucosal involvement is more common in patients with negative anti-Dsg-1/3 results. The severity of the lesions in most of the patients is mild at baseline and most patients seems to respond to RTX therapy and reach remission.

Pigmented purpuric dermatoses versus purpuric mycosis fungoides: Clinicopathologic similarities and new insights into dermoscopic features.

BACKGROUND: The diagnosis of purpuric mycosis fungoides (PMF) is often challenging to be clinically differentiated from inflammatory diseases such as pigmented purpuric dermatosis (PPD). Dermoscopy as a non-invasive method can be employed for the visualisation of features invisible to the naked eye. OBJECTIVES: This study aimed to survey the dermoscopic findings of PMF in comparison with PPD. METHODS: Forty-one patients with an established diagnosis of PMF (n = 28) and PPD (n = 13) were prospectively recruited. Dermoscopic images were taken by FotoFinder Medicam 1000 (FotoFinder Systems GmbH, Bad Birnbach, Germany). RESULTS: Characteristic dermoscopic patterns consisting of fine short linear vessels (35.7%, P = 0.017) and spermatozoa-like structures (50%, P = 0.014) were found to be significantly more common in PMF lesions, while PPD lesions were typified by erythematous globules (76.9%, P = 0.01), in the background colour of dull red (61.5%, P = 0.01) and reticular pigmentation (61.5%, P = 0.044). CONCLUSIONS: This study showed the usefulness of dermoscopy for the diagnosis of PMF and PPD cases. Studies with long-term follow-up are needed to affirm the value of these dermoscopic patterns in the differentiation between the two entities.

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.

The Serum Level of Oxidative Stress and Antioxidant Markers in Patients with Psoriasis: A Cross-sectional Study.

BACKGROUND: soriasis is a chronic, immune-mediated, inflammatory disease. Previous studies have indicated a possible role of oxidative stress in the pathogenesis of psoriasis. OBJECTIVE: We sought to compare special oxidative stress and antioxidant markers in psoriatic patients. METHODS: This study included 35 patients with psoriasis and 35 healthy controls. Serum levels of oxidant markers, including advanced glycation end products (AGEs) and advanced oxidation protein products (AOPPs), as well as antioxidant enzymes, including lecithin-cholesterol acyltransferase (LCAT), paraoxonase-1 (PON1), and ferric-reducing ability of plasma (FRAP), were measured. RESULTS: The mean age of the subjects was 39.63±13 years in the case group and 39.37±12.62 years in the control group (p=0.92). The mean Psoriasis Area and Severity Index (PASI) scores of these groups were 15.27 and 10.47. The mean levels of fasting blood sugar and C-reactive protein were significantly higher in the case group than the control group (p=0.04 and p=0.02, respectively). Moreover, the mean levels of AGEs and AOPPs in the case group were significantly higher than in the control group (p=0.001), while the mean levels of FRAP, PON1, and LCAT were significantly lower in the case group than in the control group (p=0.001). There was no significant association between PASI and oxidant or antioxidant markers, except for AOPP, which had a negative association with PASI. CONCLUSION: Our findings suggest an imbalance among oxidative stress and antioxidant markers in the pathogenesis of psoriasis. The oxidant-antioxidant enzymatic system is impaired in psoriasis as a result of increased oxidant products and reduced antioxidant activity.

Oral simvastatin combined with narrowband UVB for the treatment of psoriasis: A randomized controlled trial.

Psoriasis is a common chronic skin condition, which is an immune-related hyperproliferative disorder. Among the different treatments for psoriasis, statins have been found to reduce the severity of the disease. Accordingly, fluvastatin and simvastatin are known to have anti-inflammatory effects by inhibiting inflammatory cytokines and lymphocyte function. Narrowband ultraviolet B (NB-UVB) is known as an effective and safe modality for psoriasis treatment. In this double blind, randomized controlled trial, we investigated the efficacy and safety of adding simvastatin to NB-UVB phototherapy in patients with psoriasis. Forty-eight patients with psoriasis undergoing NB-UVB phototherapy were randomly divided into placebo groups; one received oral simvastatin, and the other received a placebo for 12 weeks. Psoriasis severity was assessed with the Psoriasis Area and Severity Index (PASI) and Dermatology Life and Quality Index (DLQI). Both groups showed a significant decline in PASI score after 6 and 12 weeks compared to the baseline. The differences in reducing PASI score and DLQI between the two groups were not significant neither at week sixth nor 12th. In addition, DLQI decreased significantly in the placebo group at week 12th. In contrast with previous studies, we did not find any additional effects for oral simvastatin5 in treating psoriasis with NB-UVB. Also, an insignificant difference in the improvement of quality of life between both groups was ascertained.

Decreased Serum Levels of Interleukin-4 and Interleukin-21 in New Pemphigus Vulgaris Patients, but Not Chronic Patients With Inactive Disease Compared to Healthy Controls.

BACKGROUND: Pemphigus is a rare group of autoimmune blistering diseases with unknown etiology and unclear pathogenesis. Pemphigus vulgaris (PV) is the most common subtype, and is characterized by ulcerations or flaccid blisters on mucous membranes and on the skin. It is accepted that cytokines have a critical role in the pathogenesis of PV, while their exact roles remain to be elucidated. OBJECTIVES: This study assessed serum levels of interleukin (IL)-4 and IL-21 in different phases of the disease in comparison with healthy controls. METHODS: In a case-control cohort design, serum levels of IL-4 and IL-21 were determined by ELISA in three groups: patients with newly diagnosed PV, patients with chronic, inactive PV (PV in remission), and healthy controls. RESULTS: The study included 88 individuals (58 women and 30 men), including 26 with newly diagnosed PV, 33 with PV in remission, and 29 healthy controls. A significant difference was found among the groups for IL-21 (P = .044), but not for IL-4 (P = .374). Serum levels of IL-4 and IL-21 in newly diagnosed patients were significantly lower than in healthy controls (P = .005 for both), but these cytokine levels in patients with PV in remission were not different from those of controls (P = .343 and P = .221, respectively). Also, no differences in cytokine levels were detected between the newly diagnosed patients and patients with PV in remission. Regardless of disease phase, we detected significantly lower levels of IL-21 in patients than controls (P = .027), but no differences for IL-4 (P = .374). CONCLUSIONS: IL-4 and IL-21 are involved in PV pathogenesis and disease severity. More studies are required to clarify the role of IL-4 and IL-21 in immunopathogenesis and immune response during PV.

Hypertension in psoriasis patients: based on office and ambulatory blood pressure measurement.

OBJECTIVE: Psoriasis is a chronic inflammatory disorder, which is associated with high risk of metabolic comorbidities. Hypertension (HTN) is among the most common and serious associations. In this study, we aimed to evaluate HTN in psoriatic patients through office and ambulatory blood pressure monitoring (ABPM). MATERIALS AND METHODS: Forty-nine patients with confirmed diagnosis of psoriasis were enrolled in the study. Office measurement of blood pressure was performed and then holter monitoring was used for 24-h ABPM. RESULTS: Thirty-six patients (73.4%) had HTN including 13 females (36.1%) and 23 males (63.9%) (P = 0.011). Twelve patients (33.3%) had masked HTN (six females and six males). Office, 24-h, morning, daytime, and nocturnal HTN were present in 49%, 40.8%, 34.7%, 36.7%, and 63.3% of our patients, respectively. The only factor significantly related to morning/daytime/24 h HTN was age, which hypertensive patients had higher age. About 22.4% of patients had metabolic syndrome, which was significantly associated with FBS, weight, waist circumference, and BMI. CONCLUSION: Psoriasis is associated with a high rate of HTN. Masked HTN constitutes nearly one-third of hypertensive patients. ABPM increases the accuracy of HTN detection in psoriatic patients.

Adverse electrocardiographic effects of rituximab infusion in pemphigus patients.

Pemphigus encompasses a group of chronic autoimmune blistering diseases of the skin and/or mucosa. Rituximab (RTX) has shown promising efficacy for the treatment of pemphigus in the past decade. Considering potential cardiac side effects, this study was conducted to assess the effects of RTX on electrocardiogram (ECG) parameters in pemphigus patients. This observational cross-sectional study was conducted in 80 consecutive patients with pemphigus who were eligible for RTX infusion. The patients' heart rhythm was monitored before, during and after RTX infusion and ECG parameters were compared before and after the infusion. Eighty patients were included in the study. The median age of the patients was 42 years. The mean and maximum heart rate (HR) increased significantly after RTX infusion compared with pre-infusion mean and maximum HR. The mean corrected QT (QTc) interval, premature atrial contraction (PAC), and premature ventricular contraction (PVC) counts increased significantly after RTX infusion (P value: 0.009, 0.004 and 0.007 respectively). According to the results of this study, RTX has potential arrhythmogenic side effects including increased mean and maximum HR, QTc interval, PAC and PVC count. However, these findings are minor and should not prevent eligible patients from receiving RTX infusion.

Crusted Scabies Complicated with Herpes Simplex and Sepsis.

Crusted scabies is a rare and extremely contagious infestation by Sarcoptes scabiei. Kaposi's varicelliform eruption (KVE) refers to herpes simplex virus infection superimposed on pre-existing dermatosis such as atopic dermatitis, Darier's disease, and pemphigus. We report a case of KVE superimposed on crusted scabies in a middle-aged woman. Her condition was complicated with sepsis. She was treated with IV meropenem, vancomycin, and acyclovir and was released 2 weeks later in good condition. To our knowledge, only rare cases of crusted scabies complicated by KVE have been reported.

Decreased serum levels of interleukin-17, interleukin-23, TGF-ß in pemphigus vulgaris patients, and their association with disease phase.

The exact pathogenesis of Pemphigus Vulgaris (PV) has remained unclear, but it seems that cytokines play critical roles in this disease. This study aims to assess the serum levels of interleukin (IL)-6, IL-17, IL-23, and TGF-ß in PV patients and compare the results to the healthy controls. Serum levels of IL6, IL-17, IL-23, and TGF-ß were successfully determined by enzyme-linked immunosorbent assay (ELISA) in 27 newly diagnosed PV, 32 patients in remission, and 29 healthy controls. It was shown that the mean serum levels of IL-17, IL-23, and TGF-ß serum are significantly different among the PV patients and healthy controls (P values: <.001, .001, and .003, respectively). It was found that new PV patients have lower serum levels of IL-17, IL-23, and TGF-ß as compared to healthy controls (P values: <.001, <.001, and .003, respectively). Regarding IL-6, no significant difference was observed between the healthy controls and the other two groups of patients. IL-17, IL-23, and TGF-ß are involved in the pathogenesis of PV. However, more studies are required to clarify their exact roles in the immunopathogenesis of PV.

Granuloma annulare after Botulonium toxin A injection: A rare association.

BACKGROUND: Botulinum toxin is generally considered safe and has been used in constantly expanded cosmetic and therapeutic indications. However, long-term side effects such as granulomatous reactions have been associated with this drug. AIMS: We aim to evaluate a rare reaction to Botulonium toxin A injection. PATIENTS/METHODS: A 44-year-old woman, developed annular plaques eleven months after botulinum toxin A injection for the correction treatment of wrinklesglabellar rhytides. RESULTS: Histopathological examination revealed granuloma annulare formation. Clinical and biological investigations were negative, ruling out the hypothesis of systemic sarcoidosis. Triamcinolone acetonide injection was followed by a regression of the plaques. CONCLUSION: There are previous reports in the literature of sarcoidal and foreign body granuloma at the sites of injection of botulinum toxin A injection. To our knowledge this is the first report of granuloma annulare occurrence after botulinum toxin A injection.