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.

Drug-induced cutaneous pseudolymphoma: A systematic review of the literature.

Drug-induced cutaneous pseudolymphoma (CPL) is a common form of pseudolymphoma and there are numerous drugs associated with it. In this study, we performed a systematic review of the literature by searching PubMed/Medline and Embase databases to determine the most common drugs responsible for CPL and to define the demographic, clinical, histopathological and immunopathological characteristics of patients (updated on 30 December 2020). From 883 initially found articles, 56 studies (89 reported cases) were included. The mean age of patients was 54.4 ± 17.7 (ranging 8-86) years, and 46 (51.7%) were men. The median time interval between drug intake and CPL occurrence was 120 days (range 1-7300 days). The shortest median time interval between taking the drug and the onset of the disease was observed among patients taking antidepressants (60 days) (range 7-540) and the longest median time interval was observed in individuals using immunomodulators (300 days) (range 3-7300). The most-reported drug categories causing CPL were anti-hypertensives (17.9%), anticonvulsants (14.6%), monoclonal antibodies (13.4%) and antidepressants (11.2%). Moreover, the most common drugs were phenytoin (6.7%), amlodipine (5.6%), fluoxetine (5.6%) and carbamazepine (4.4%). Histopathological evaluation of 76 cases revealed 62 (81.5%) reports of T-cell infiltrations. Furthermore, positive reports of CD4 (94.0%), CD8 (93.0%) and CD30 (87.5%) were noted. The lowest prevalence of CD30-positive reports was observed among monoclonal antibodies. In conclusion, anti-hypertensives, anti-convulsants, monoclonal antibodies and anti-depressants are the most common drugs responsible for CPL. It mostly presents in middle-aged patients with almost no gender difference as pruritic papules, nodules and plaques.

Immunological aspects of COVID-19-related skin manifestations: Revisiting pathogenic mechanism in the light of new evidence.

The newly emerged coronavirus disease 2019 (COVID-19), induced by a novel strain of the coronavirus family, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a rapidly spreading global threat. This virus affects a fair number of tissues in the human body by availing itself of potential target receptors like Angiotensin-Converting Enzyme 2 (ACE2). Presenting with diverse clinical manifestations, COVID-19 has raised the urge for extensive research in different medical fields, including dermatology. Developing a comprehensive knowledge of cutaneous manifestations is highly important as it can help us in early diagnosis and better management of the ongoing pandemic. The dermatological presentations of COVID-19 are classified into main categories of vascular and non-vascular (exanthematous) patterns. Though not yet fully confirmed, the pathogenesis of these cutaneous presentations has been suggested to be more related to the overactivation of the immune system. In this review, we discuss in detail the clinical features of the diverse skin lesions in COVID-19 patients and the imperative role of the immune system in their pathogenesis and development. Furthermore, we will discuss the reasons behind the accentuation of skin lesions in COVID-19 compared to the same virus family predecessors.

Retrospective study of gingival involvement in pemphigus: A difficult to treat phenomenon.

Pemphigus is a group of autoimmune diseases characterized by flaccid lesions on the skin and mucous membranes. In pemphigus vulgaris, the most common subtype of pemphigus, lesions might be appeared anywhere on the oral mucosa, mostly in the buccal mucosa. However, the gingiva is a less frequently affected site. Here, we performed a retrospective study at Tehran University of Medical Sciences, covering a two-year period to identify pemphigus patients with active lesions confined to the gingiva. Considering 1787 initially evaluated pemphigus cases, 512 (28.6%) were found to have a history of gingival involvement. Among them, 31 patients had only gingival involvement during their last visit, including 29 (93.5%) women and only two (6.5%) men. The mean of disease duration in this group was 5.29 ± 3.46 years, and they had gingival involvement for a mean of 23.9 ± 19.3 months. Of 28 patients, nine were negative for anti-Dsg3 and 24 were negative for anti-Dsg1. In 24 patients, who received rituximab, the mean pemphigus disease area index specifically for gingiva was 4.76 ± 0.74 at baseline, which had changed to 4.13 ± 0.75 and 3.26 ± 0.63 three and 6 months after rituximab administration, respectively. After 3 months, gingival lesions were either entirely resolved (n = 3), partially resolved (n = 11), remained unchanged (n = 2), or progressed (n = 7). Gingiva-confined presentation of lesions in pemphigus could be non-anti-Dsg1/3 dependent in some patients. Such patients do not respond well to conventional treatments and rituximab therapy. More studies on the pathogenesis of gingiva-confined presentation of pemphigus are required.

Evaluating the risk-to-benefit ratio of using cotrimoxazole as a pneumocystis pneumonia preventative intervention among pemphigus patients treated with rituximab: A retrospective study with 494 patients.

Rituximab is widely used as the first-line treatment for pemphigus patients. Since it depletes the B cells, it increases the risk of infections. Here, we evaluated the prophylactic efficacy of cotrimoxazole in decreasing the risk of pneumocystis pneumonia (PCP) infection in the pemphigus patients treated with rituximab. The medical records of confirmed pemphigus patients receiving rituximab were evaluated in two groups; those who received cotrimoxazole as a prophylactic after rituximab and patients who only received rituximab without any prophylaxis. The occurrence of PCP infection was determined in each group and compared. Medical records of 494 patients, including 301 women and 193 men, with the mean age of 46.74 years were analyzed. The phenotypes of the disease were mucocutaneous (n = 364), mucosal (n = 88), and cutaneous (n = 42). Among them, 235 cases had received cotrimoxazole as a prophylaxis and 259 patients did not. The incidence of PCP in total patients was 2 (0.4%), one in each group. Accordingly, no significant difference was observed in the incidence of PCP between two groups (p = 0.84). Also, no cotrimoxazole-related side effect was observed in the treated group. It seems that due to the low incidence of PCP in pemphigus patients treated with rituximab, prophylactic cotrimoxazole therapy is not necessary and it only increases the overall therapy cost and might cause cotrimoxazole-related adverse effects in some patients. However, regarding its probable beneficial effect in patients with long-term history of immunosuppressive therapy, more studies are required.

Prevalence and management of chronic hepatitis B in pemphigus and pemphigoid patients: New evidence for the safety of rituximab.

Although the treatments of pemphigus and pemphigoid patients have tended toward safer options, patients with chronic infections seem to be still at the risk of infection reactivation when they are exposed to any of immunosuppressive treatments. A retrospective study on 1646 registered pemphigus and pemphigoid patients was conducted between January 2017 and February 2019 and the prevalence of HBV, the association between the treatments, mainly prednisolone and rituximab with HBV reactivation as well as outcomes of patients after management with antiviral therapies were evaluated. From 1646 reviewed patients, 10 (0.60%) patients with chronic HBV were identified. We found a negative correlation between the ALT (p-value<0.001), AST (p-value = 0.090), and Pemphigus Disease Area Index (PDAI) (p-value = 0.034) and age of patients. At the time points that prednisolone dosage was higher, higher levels of ALT, but no difference in AST levels was noted. The portion of patients with normal ALT was significantly higher (p-value = 0.036; OR = 2.22) in those who had received rituximab within the previous 6 months (38 of 49; 77.6%) as compared to those who did not (81 of 133; 60.9%). We concluded that avoidance (high dose) systemic corticosteroids in patients with chronic HBV, and using rituximab instead in severe cases benefit this group of patients.

Punctate Pattern and Pemphigus: Is There Any Evidence of Punctate Pattern Among Iranian Patients?

AIM: To examine the prevalence of this novel pattern among Iranian patients with pemphigus and peruse the relationship between the presence of a punctate pattern with clinical severity of disease and histopathological findings. METHODS: One hundred recently diagnosed patients with pemphigus were enrolled. DIF evaluation and routine light microscopy were performed on their biopsy specimens. Disease severity was determined using the Pemphigus Disease Area Index. Serum samples were collected to measure autoantibody titers using enzyme-linked immunosorbent assay. RESULTS: All the samples evaluated by DIF showed a continuous linear pattern of intercellular IgG deposition, whereas none of them had a punctate pattern. Despite a significant correlation between the Pemphigus Disease Area Index score and autoantibody values, no association between histopathological findings and disease severity has been found. CONCLUSION: We could not detect any punctate pattern among Iranian patients with pemphigus. The importance of this pattern in the diagnosis of pemphigus might be different among patients with different ethnic and genetic factors.

Genetics and genomics of SARS-CoV-2: A review of the literature with the special focus on genetic diversity and SARS-CoV-2 genome detection.

The outbreak of 2019-novel coronavirus disease (COVID-19), caused by SARS-CoV-2, started in late 2019; in a short time, it has spread rapidly all over the world. Although some possible antiviral and anti-inflammatory medications are available, thousands of people are dying daily. Well-understanding of the SARS-CoV-2 genome is not only essential for the development of new treatments/vaccines, but it also can be used for improving the sensitivity and specificity of current approaches for virus detection. Accordingly, we reviewed the most critical findings related to the genetics of the SARS-CoV-2, with a specific focus on genetic diversity and reported mutations, molecular-based diagnosis assays, using interfering RNA technology for the treatment of patients, and genetic-related vaccination strategies. Additionally, considering the unanswered questions or uncertainties in these regards, different topics were discussed.

Risk Factors of COVID-19 Associated Mucormycosis (CAM) in Iranian Patients: A Single-Center Retrospective Study.

BACKGROUND: COVID-19 associated mucormycosis (CAM) has been known as one of the most severe post-COVID morbidities. OBJECTIVES: To describe CAM cases, identify possible risk factors, and report outcomes of patients. METHODS: This retrospective study was performed in Amir-Alam Hospital, Tehran, Iran between February 2020 and September 2021. Patients with mucormycosis who had an active or previous diagnosis of COVID-19 have been included. RESULTS: Of 94 patients with mucormycosis, 52 (33 men and 19 women; mean age: 57.0 ± 11.82 years) were identified with an active or history of COVID-19. Rhino-orbital, rhino maxillary, rhino-orbito cerebral subtypes of mucormycosis were detected in 6 (11.5%), 18(34.6%), and 28(53.8%) patients. As a control group, 130 (69 men and 61 women; mean age: 53.10 ± 14.49 years) random RT-PCR-confirmed COVID-19 patients without mucormycosis have been included. The mean interval between COVID-19 diagnosis and initial mucormycosis symptoms was 16.63 ± 8.4 days (range 0-51). Those in the CAM group had a significantly more severe course of COVID-19 (OR = 3.60, P-value < 0.01). Known history of previous diabetes mellitus (OR = 7.37, P-value < 0.01), smoking (OR = 4.55, P-value < 0.01), and history of receiving high-dose corticosteroid pulse therapy because of more severe COVID-19 (P-value = 0.022) were found as risk factors. New-onset post-COVID hyperglycemia was lower in the CAM group (46.2% vs. 63.8%; OR = 0.485, P-value = 0.028). After treatment of the CAM group, 41(78.8%) of patients recovered from mucormycosis. The mean ages of the expired patients in the CAM group were significantly higher than those who recovered from mucormycosis (66.18 ± 9.56 vs. 54.56 ± 11.22 years; P < 0.01); and COVID-19 disease was more severe (P = 0.046). CONCLUSION: Either active or history of COVID-19 can cause an increase in the risk of mucormycosis development. Some of the most important risk factors are the medical history of diabetes mellitus, smoking, and high-dose corticosteroid therapy. CAM is important possible comorbidity related to COVID-19, which could make the post-COVID conditions more complicated. More research and studies with greater sample sizes among different ethnicities are needed to explore the association between COVID-19 and mucormycosis.

Direct N- or C-Terminal Protein Labeling Via a Sortase-Mediated Swapping Approach.

Site-specific protein labeling is important in biomedical research and biotechnology. While many methods allow site-specific protein modification, a straightforward approach for efficient N-terminal protein labeling is not available. We introduce a novel sortase-mediated swapping approach for a one-step site-specific N-terminal labeling with a near-quantitative yield. We show that this method allows rapid and efficient cleavage and simultaneous labeling of the N or C termini of fusion proteins. The method does not require any prior modification beyond the genetic incorporation of the sortase recognition motif. This new approach provides flexibility for protein engineering and site-specific protein modifications.

Remdesivir: A beacon of hope from Ebola virus disease to COVID-19.

Since the emergence of coronavirus disease 2019 (Covid-19), many studies have been performed to characterize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and find the optimum way to combat this virus. After suggestions and assessments of several therapeutic options, remdesivir (GS-5734), a direct-acting antiviral drug previously tested against Ebola virus disease, was found to be moderately effective and probably safe for inhibiting SARS-CoV-2 replication. Finally, on 1 May 2020, remdesivir (GS-5734) was granted emergency use authorization as an investigational drug for the treatment of Covid-19 by the Food and Drug Administration. However, without a doubt, there are challenging days ahead. Here, we provide a review of the latest findings (based on preprints, post-prints, and news releases in scientific websites) related to remdesivir efficacy and safety for the treatment of Covid-19, along with covering remdesivir history from bench-to-bedside, as well as an overview of its mechanism of action. In addition, active clinical trials, as well as challenging issues related to the future of remdesivir in Covid-19, are covered. Up to the date of writing this review (19 May 2020), there is one finished randomized clinical trial and two completed non-randomized studies, in addition to some ongoing studies, including three observational studies, two expanded access studies, and seven active clinical trials registered on the clinicaltrials.gov and isrctn.com websites. Based on these studies, it seems that remdesivir could be an effective and probably safe treatment option for Covid-19. However, more randomized controlled studies are required.

Rituximab in practice: Clinical evaluation of patients with pemphigus after rituximab administration.

Pemphigus Vulgaris (PV) is a rare autoimmune blistering disease, which mainly causes mucosal and/or cutaneous lesions. In June 2018, FDA approved Rituximab (RTX)-a B-cell depleting agent-for the management of patients with moderate-to-severe pemphigus. Although the majority of patients respond well to this drug, some do not reach complete remission with a single cycle of RTX. In this review, following an overview of RTX and its clinical outcomes, we have focused on the possible outcomes after RTX therapy in patients with PV. The response is defined into four main categories; complete responders, partial responders, nonresponders, and paradoxical reactions, based on three possibilities of reaching the consolidation phase after 3 months, reaching remission until 6 months, and the ability of corticosteroid tapering in 6 months after RTX administration. Concerning the safety of RTX, three categories of infusion reactions, short and long-term side effects are discussed. Additionally, we have suggested approaches for the evaluation of clinical and serological responses at different critical time-points, including 1, 2, 3, and 6 months after RTX administration. Finally, available markers to predict the response to RTX and research gaps in the field of RTX therapy have been summarized.

A systematic review on efficacy, safety, and treatment-durability of low-dose rituximab for the treatment of Pemphigus: special focus on COVID-19 pandemic concerns.

BACKGROUND: Rituximab is a FDA-approved monoclonal antibody for adults with moderate to severe potentially life-threatening pemphigus vulgaris. Recent studies have focused on assessments of efficacy and safety of low-dose rituximab (<2 gram in each cycle). METHOD: Databases were searched from 2010 to 2020 (last update: 1 June 2020). RESULT: Nine studies were entered; including180 cases (92: women, 88: men, age range: 9-83 years). The dosages of each Rituximab cycle varied between ultra-low-dose (≤500 mg for a cycle, either multiple infusions or a single infusion), low-dose (2 × 375 mg/m2 or 2 × 500 mg) and modified-dose (3 × 375 mg/m2 or 3 × 500 mg). The efficacy and safety of Rituximab in the studies are known by the recovery time, relapse time, and side events. According to the studies, 2 × 500 can lead to complete remission in a broad range, from 35 to 82%. These differences might be explained by different end-points and variable cumulative corticosteroid dosage after RTX administration. Although the studies showed that low dose RTX is efficient, there are some controversies regarding the choosing low-dose for severe patients. CONCLUSION: Considering the effectiveness of low-dose, intermediate dose, and ultra-low-dose protocols of Rituximab in inducing remission in pemphigus disease and considering factors such as cost of therapy, and the need to induce a minimum of immunosuppression for a minimum duration in the COVID-19 pandemic, suggested to use low-dose Rituximab protocol (2 infusions of 500 mg Rituximab: interval of 2 weeks) to induce the remission in mild-to-moderate pemphigus patients.

Pathogenic and protective roles of cytokines in pemphigus: A systematic review.

Pemphigus is a rare and life-threatening group of blistering autoimmune diseases that affects the skin and mucous membranes. There are two major subtypes of pemphigus, including pemphigus vulgaris (PV) and pemphigus foliaceus (PF); each has different clinical manifestations. Pemphigus cannot be considered as a single disease and each patient may have a specific immunological profile. There are a lot of studies available regarding the role of different cytokines in the pathogenesis of pemphigus, although the data are not coherent between different studies. In this study, a systematic review from inception to December 25, 2019, through the MEDLINE/PubMed database had been performed to address several aspects of cytokines' roles in PV and PF. As a result, 57 studies from 352 initially found records, containing 26 cytokines had met the inclusion criteria. We found different pieces of evidence in favor of increased levels of TNF-α, TGF-ß, interleukin (IL)-8, IL-10, IL-12, IL-17, IL-21; while decreased levels of IL-2 and IL-23 in pemphigus patients. Regarding other cytokines, such as IFN-γ, IL-5, IL-15, IL-22, there are controversial results. Different studies suggested the association of TNF-α and IL-6 with disease activity and autoantibodies values. However, there is uncertainty regarding the role of IFN-γ, IL-2, IL-15, IL-27, and IL-33. Treatments with immunosuppressive agents may decrease IL-1, IL-6, IL-8, IFN-γ, IL-33, IL-17 levels. In conclusion, cytokines are deeply involved in PV and PF pathogenesis, and targeting specific cytokines may lead to development of more promising treatments for pemphigus.

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.

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.

Single-nucleotide polymorphisms associated with pemphigus vulgaris: Potent markers for better treatment and personalized medicine.

Pemphigus vulgaris (PV) is a rare autoimmune blistering disorder, which could affect both skin and mucosal surfaces. There is increasing evidence that genetics plays a critical role in PV development, severity and prognosis. Single-nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people and have been widely evaluated in most diseases. However, there are few studies regarding the roles of SNPs in the PV. Here, we reviewed both pathogenic and protective roles of the SNPs in non-HLA genes regarding the PV. Among the large number of studied SNPs, it was found that several SNPs in different genes might control the susceptibility of PV, including TNFA (rs361525, rs1800629, rs1800629), IL10 (rs1800871, rs1800896, rs1800871, and rs1800872), IL6 (rs1800795), CTLA4 (rs231775), ICOS (rs10932029), CD86 (rs1129055), DSG3 (rs8085532, rs3911655, rs3848485, rs3794925, rs1466379), ST18 (rs2304365, rs17315309) and TAP2 (rs7454108), probably in a population-specific manner. Moreover, SNPs in glucocorticoid receptor, also known as nuclear receptor subfamily 3 group C member 1 (NR3C1) gene, including rs11745958, rs17209237, rs33388, rs7701443 as well as rs116855232 at NUDT15, seem to be associated with therapeutic outcomes in PV patients. Additionally, variations in the other genes involved in the drugs' metabolisms, pharmacokinetics and pharmacodynamics such as rs396991 in FCGR3A gene could be used for the prediction of clinical response to drugs and side effects. Taken together, SNPs seem to be valuable tools for better management of PV patients. Further studies need to be conducted to evaluate SNPs in genes that control immune responses and apoptosis.

Estimated cut-off values for pemphigus severity classification according to pemphigus disease area index (PDAI), autoimmune bullous skin disorder intensity score (ABSIS), and anti-desmoglein 1 autoantibodies.

BACKGROUND: Pemphigus is a potentially fatal disease if left untreated. Valid scoring systems and defined cut-off values for classification of patients would help with better management through specified pharmaceutical and non-pharmaceutical treatments. METHODS: In this study, pemphigus patients who were receiving immunosuppressive treatments and had recent disease relapse were recruited for examination of pemphigus disease area index(PDAI), autoimmune bullous skin disorder intensity score (ABSIS), physician global assessment (PGA), autoimmune bullous disease quality of life (ABQoL), anti-desmoglein 1 (anti-Dsg1), and anti-Dsg3 autoantibody titers from December-2017 to February-2018. Cut-off values were estimated using model-based clustering classification and the 25th and 75th percentiles approach, performed separately for the exclusive cutaneous, exclusive mucosal, and mucocutaneous groups. RESULTS: In the 109 included patients, the 25th and 75th percentiles cut-offs were 6.2 and 27 for PDAI score, and 4 and 29.5 for ABSIS score. The model-based analysis resulted in two groups (cut-point:15) for PDAI score, and three groups (cut-points:6.4 and 31.5) for ABSIS score. The groups were significantly different for the PDAI, ABSIS, PGA, and ABQoL values. Based on anti-Dsg1 autoantibody values, the model-based analysis cut-point was 128 and the 25th and 75th percentiles cut-offs were 98 and 182. Anti-Dsg3 autoantibody values did not differentiate between pemphigus severity classes. CONCLUSIONS: Estimated cut-off values based on the anti-Dsg1 level, PDAI, and ABSIS scoring systems could be used to classify patients into different severity grades for better management and prognosis.

The elevated level of osteopontin in patients with pemphigus vulgaris: A cytokine-like protein with a therapeutic potential.

BACKGROUND: Pemphigus vulgaris (PV) is a life-threatening autoimmune disease with no certain treatment. Anticytokine therapy is being increasingly discussed in multiple autoimmune diseases. Osteopontin (OPN) is a glycoprotein produced by a variety of immune cells. Increased OPN serum levels have been reported in several autoimmune diseases, with targeting OPN considered as a promising therapy in these diseases. However, the role of OPN in PV has not been well studied so far. OBJECTIVE: To investigate whether OPN level is elevated in PV patients in the active stage of the disease and to examine its possible relationship with disease severity and anti-desmoglein (anti-Dsg) antibodies levels. MATERIALS AND METHODS: This study included 53 consecutive subjects affected by PV and 38 age- and sex-matched healthy controls. Clinical characteristics and Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) were assessed. Serum OPN levels (pg/mL) and anti-Dsg antibodies were also measured. RESULTS: The serum OPN level of the patient group proved to be statistically higher than that of the control group (11.08 ± 5.24 vs 8.47 ± 5.68; p = .02). No significant relationship were detected between the serum OPN level and anti-Dsg1 or anti-Dsg3 antibodies (r = 0.1, p = .2 and r = 0.1, p = .4), respectively. In addition, no correlation was found between serum OPN levels and severity of PV as measured by ABSIS (r = 0.08 and p = .5). CONCLUSION: The growth observed in OPN levels in pemphigus patients suggests the role of OPN in pemphigus pathogenesis, but there is a need for more extensive studies to show how OPN can be associated with the PV pathogenesis and whether OPN could be used as an important therapeutic target in pemphigus disease.

Iranian guideline for rituximab therapy in pemphigus patients.

Pemphigus vulgaris (PV) is an autoimmune blistering disease affecting the skin and/or mucosa. Rituximab (RTX) has been approved recently by US FDA as an effective and safe treatment of PV. The high incidence of PV in Iran encouraged our team to prepare a consensus guideline for RTX administration based on literature review and a decade experience of an expert panel. RTX is recommended for the treatment of new cases of PV as well as patients not responding to conventional therapy. Contraindications include history of anaphylaxis or IgE-mediated hypersensitivity to murine proteins of RTX, severe active infections, pregnancy, breastfeeding, severe heart failure, and arrhythmia. Prophylactic antiviral therapy is recommended in patients at risk of reactivation of HBV and isoniazid for those at risk of reactivation of tuberculosis. Concomitant use of systemic corticosteroids is recommended as a rule. Except for methotrexate, the combination with other immunosuppressive drugs is discouraged. Intravenous immunoglobulin is recommended for those at risk of infections or with extensive disease. The recommended dosage of RTX for the first cycle is 2 g either 500 mg weekly or 1 g biweekly. There is no general consensus whether the next doses of RTX be administered upon relapse or as maintenance therapy. We strongly recommend RTX sooner in the course of pemphigus.