A systematic review and clinical atlas on mucocutaneous presentations of the current monkeypox outbreak: With a comprehensive approach to all dermatologic and nondermatologic aspects of the new and previous monkeypox outbreaks.

Monkeypox is a zoonotic disease, endemic in central and west African regions, and has re-emerged, currently causing an outbreak as of May 2022. In this systematic review, we aimed to characterize the current face of the disease, with a detailed categorization of mucocutaneous, as well as systemic symptoms of the disease. We searched four main online databases with the keywords "monkeypox" and "Orthopoxvirus". A total of 46 articles were included, with a cumulative number of 1984 confirmed cases. Patients were predominantly men who have sex with men, who were mostly in their 30s, with a history of unprotected sexual contact or international travel. Among mucocutaneous manifestations, anogenital lesions were the most commonly observed, followed by lesions on the limbs, face, trunk, and palms or soles. Among lesion types, vesiculopustular, pustular or pseudo-pustular, vesicular-umbilicated and papular lesions were the most common, mainly presenting asynchronously, with less than 10 lesions on each patient. Almost all patients also reported systemic manifestations, namely fever, lymphadenopathy, fatigue, myalgia, headaches, pharyngitis, and proctitis. Sexual contact is the main pathway of transmission in the current outbreak, with viral shedding in bodily fluids playing a key role. We've compared these idiosyncratic findings of the new outbreak with previous outbreaks. We've also gathered and categorized images from our included studies to make a "clinical atlas" for this "new" face of monkeypox, which can be of utmost importance for clinicians to be familiarized with, and have a clear picture of monkeypox for their differential diagnoses.

A systematic review on efficacy, safety and treatment durability of intravenous immunoglobulin in autoimmune bullous dermatoses: Special focus on indication and combination therapy.

Autoimmune bullous diseases (AIBDs) are a group of rare blistering dermatoses of the mucous membrane and/or skin. The efficacy, safety and treatment durability of intravenous immunoglobulin (IVIg) as an alternative treatment should be explored to systematically review the available literature regarding treatment outcomes with IVIg in AIBD patients. The predefined search strategy was incorporated into the following database, MEDLINE/PubMed, Embase, Scopus and Web of Science on 18 July 2022. Sixty studies were enrolled using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The use of IVIg alone or combined with rituximab was reported in 500 patients with pemphigus, 82 patients with bullous pemphigoid, 146 patients with mucous membranes pemphigoid and 19 patients with epidermolysis bullosa acquisita. Disease remission with IVIg therapy and RTX + IVIg combination therapy were recorded as 82.8% and 86.7% in pemphigus, 88.0% and 100% in bullous pemphigoid and 91.3% and 75.0% in mucous membrane pemphigoid, respectively. In epidermolysis bullosa acquisita, treatment with IVIg led to 78.6% disease remission; no data were available regarding the treatment with RTX + IVIg in this group of patients. Among all the included patients, 37.5% experienced at least one IVIg-related side effect; the most common ones were headaches, fever/chills and nausea/vomiting. The use of IVIg with or without rituximab had a favourable clinical response in patients with AIBDs. IVIg has no major influence on the normal immune system, which makes its utilization for patients with AIBDs reasonable.

Striae gravidarum treatment: evaluating non-ablating fractional laser (NAFL) efficacy and safety.

BACKGROUND: Striae gravidarum (SG) is a common pregnancy-related dermatologic problem, for which finding an effective treatment remains a challenge. AIM: To evaluate the safety and efficacy of 1540 nm non-ablative fractional laser (Star lux 500) in the treatment of SG in Iranian women and peruse the relationship between clinical improvement rate and patient characteristics as well as clinical features of striae. METHOD: A prospective before-after study was conducted on 50 patients with SG who received three monthly sessions of 1540 nm non-ablative fractional laser and were followed for 2 months after the last treatment session. Clinical changes were measured using both provider-rated outcome through before/after pictures represented by final clinical score (from 0 to 5) and patient-reported outcome (patient global assessment or PGA). RESULTS: Over the course of the study both final clinical score and PGA increased significantly from week 4 to week 20 (P value: <0.001 and 0.048, respectively). Only modest adverse effects including erythema, edema and hyperpigmentation were noted. CONCLUSION: In conclusion, patients with SG of different type (rubra/alba) or maturity may somehow benefit from treatment with NAFL experiencing minimal transient side effects.Therefore, NAFL may be considered a safe and partially effective treatment option for stretch mark of patients with SG.

Is skin autofluorescence a novel non-invasive marker in diabetes? A systematic review and meta-analysis of case-control studies.

Background: The advanced glycation end product (AGE) is produced from the nonenzymatic reaction between glucose and macromolecules by aging. Accumulation of AGE causes functional and structural changes in body proteins that lead to impairment of tissue protein functions. We aimed to validate AGE measurement by skin autofluorescence (SAF) in diabetes mellitus (DM) compared to the nondiabetes population. Materials and Methods: We searched the PubMed, Cochrane, and Scopus databases from their inception till September 18, 2022, for casecontrol studies measuring AGE by SAF. Nonhuman studies, as well as review articles, study proposals, editorials, case reports, or congress posters, were excluded. We used a random effects model to assess the standard mean difference (MD) of age, body mass index (BMI), HbA1c, and SAF between diabetes and nondiabetes individuals. Results: Higher SAF in DM patients indicated more accumulation of AGE compared with the nondiabetic population. Furthermore, HbA1c was considerably higher in DM patients. The MD of age, male gender, and BMI were significantly different between the DM individuals, compared with nondiabetic subjects, which can lead to altered SAF level and AGE production. There was a remarkable heterogeneity between diabetes and nondiabetes when measuring age, gender, and BMI, as well as HbA1c and SAF level. Conclusion: This study could not confirm the validity of SAF as a surrogate marker in diabetes patients. Interestingly, metabolic load and high BMI can increase SAF, considerably. Altogether, SAF could be helpful in the future as a marker for metabolic syndrome or diabetes.

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.

The role of SARS-CoV-2 infection and its vaccines in various types of hair loss.

The prevalence of hair loss has increased during COVID-19. In this study, we review the current literature on incidence and characteristics of various types of COVID-19-related and COVID-19-vaccine- related hair loss including telogen effluvium, alopecia areata, friction alopecia and anagen effluvium. Regarding most of them, the more severe the infection, the more profound and prolonged the course of alopecia. However, the most important issue is reassuring the patients of the non-serious nature of this complication, since psychological support is the most important factor in the earlier resolution of the condition.

COVID vaccination in patients under treatment with rituximab: A presentation of two cases from Iran and a review of the current knowledge with a specific focus on pemphigus.

SARS-COV2 vaccines were approved without long-term monitoring due to emergent situations. This has raised some issues about the timing and protocol of receiving vaccines in specific situations such as patients receiving immunomodulatory agents including rituximab, which is widely used for various disorders such as multiple sclerosis, pemphigus, and many rheumatologic disorders. We described two cases of pemphigus vulgaris (a new case and one with flare-up) following vaccination with Astrazeneca in Iran and reviewed the existing data in this regard through searching on PubMed, Google Scholar, and Scopus. All of the relevant papers published until June 28, 2021, which we could access their full-texts were included. We found some recommendations made by rheumatologists, neurologists, and dermatologists in regard to vaccination timing in this group of patients and tried to summarize them to provide a practical guide for clinicians. Clinicians should perform a careful, individualized risk-benefit assessment for their patients and consider a delay in rituximab administration after completion of COVID vaccination if there is not any considerable risk of disease relapse or organ failure. Moreover, choosing vaccines with potential of providing protection after single dose, especially in countries with limited access to vaccines may be a reasonable approach.

SARS-CoV-2 vaccination and practical points in psoriasis patients: A narrative review.

SARS-CoV2 vaccines were approved without long-term monitoring due to emergent situations. This has raised some issues about timing and protocol of receiving vaccines in specific situations including patients with chronic inflammatory disorders such as psoriasis. Here, we present different aspects of SARS-CoV-2 infection and vaccination in psoriasis patients and aim to provide solutions to overcome the potential challenges. In brief, the benefits of vaccination outweigh the potential risk; vaccine-triggered de novo or flares of psoriasis is uncommon. As such, all psoriasis patients, especially those receiving systemic treatments including anti tumor necrosis factor agents, are strongly recommended to get SARS-CoV-2 vaccines. It is recommended that new immunosuppressive/immunomodulatory therapies be initiated at least 1 week after the second SARS-CoV-2 vaccine dose, if possible. In addition, in severe and active forms of psoriasis, it is better to delay vaccination until stabilization of the disease.

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.

Multiple cycles of rituximab therapy for pemphigus: A group of patients with difficult- to-treat disease or a consequence of late rituximab initiation?

Pemphigus is a serious autoimmune disease with few appropriate therapeutic options. Although rituximab (RTX) has recently shown great promise in this regard, the best protocol of its administration is remains to be elucidated. This study aimed to evaluate the patients who need at least 3 cycles of treatment with RTX to identify hard-to-treat patients' characteristics, which might lead to consider more prompt protocols for treatment of them. A retrospective cross-sectional study was conducted on 45 patients with pemphigus vulgaris who received at least 3 cycles of RTX. Their demographic, clinical, and laboratory data as well as details of treatment protocol and final clinical situation of patients were evaluated. Totally, 45 patients (21 men and 24 women) with mean age of 44.33 years were included in this paper. Women were about 8 years older than men (mean age: 48.1 years versus 40.1 years, p: 0.011) and needed RTX approximately 2 years later in their course of disease (gap: 41.04 months vs. 14.85 months, p: 0.003). Buccal, truncal, and scalp regions were the most frequent sites of involvement respectively. A significant decrease in both anti-Dsg1, 3 was seen at last visit compared to baseline. However, the amount of this decrement was not significantly different between them (p: 0.083). Partial remission in 31.11%, complete remission in 24.44%, relapse in 15.56%, partial remission on treatment in 15.56% and complete remission on treatment in 13.33% were seen at the last follow-up session. RTX is an effective medication for PV even in patients with refractory disease and its therapeutic effect is increased with each subsequent cycle. Male gender, severe oral mucosal involvement on disease onset and extensive scalp and truncal lesions as first cutaneous manifestation of disease are more likely to be signs of refractory PV. Hence, it is reasonable to consider more prompt protocols for treatment of these cases. Moreover, late prescription of RTX during the course of disease might play a role in presence of more resistant form of disease.

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.

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.

High Incidence of Metabolic Syndrome Components in Lichen Planus Patients: A Prospective Cross-Sectional Study.

Background: Lichen planus (LP) is a chronic inflammatory dermatosis, involving the skin, appendages, and mucous membranes. There is a growing body of evidence about higher risk of metabolic syndrome and dyslipidemia in some dermatoses including LP. Aim: To evaluate lipid profile, leptin, and CRP status among Iranian LP patients, compared to healthy controls, and peruse the relationship between abnormal values of these parameters with the disease duration and physical characteristics of patients. Methods: 40 LP patients and 40 age- and sex-matched healthy controls were enrolled in the study. Data on weight, height, lipid profile, leptin, and CRP values were recorded and compared. Results: The mean values for leptin, CRP, and lipid profile parameters (except for HDL) were higher in patients, compared to controls. Total cholesterol level was negatively associated with disease duration in patients (P value: 0.039, r: -0.33). Serum leptin level was positively correlated with BMI both in patients and controls (P value: 0.037 and 0.003, respectively). In the patient group, LDL level, although insignificant, was higher in men, but HDL and leptin levels were significantly higher in women in comparison with men (P value: 0.018). Conclusion: Screening of LP patients in regard to their lipid profile might be more reasonable in men or those who have other cardiovascular risk factors to prevent morbidity and mortality in result of developing cardiovascular events.

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.

Do clinical severity scores correlate with the quality of life in children with psoriasis? A cross-sectional study of Iranian pediatric patients.

BACKGROUND: Psoriasis is a common chronic dermatosis that can negatively affect patients' lives. AIM: To obtain more insight about how having psoriasis and how the various clinical and physical characteristics of the disease impact the health-related quality of life (HRQoL) of pediatric patients. METHODS: A retrospective cross-sectional study was designed with 40 pediatric patients with psoriasis. HRQoL was evaluated using the Children Dermatology Life Quality Index (CDLQI). RESULTS: A total of 40 patients enrolled in this study. The mean age of participants was 12.42 ± 7.1 years (age range: 4-16 years), 21 males (52.5%), and 19 females (47.5%). The mean Psoriasis Area Severity Index (PASI) score was 8.03 ± 9.31 with a range of 0.4-25. Mean CDLQI score was 18.87 ± 8.15, indicating a considerable burden on health-related QoL. There was a strong positive correlation between CDLQI and PASI scores (p < .001, r: .653). CONCLUSION: The negative effect of psoriasis on HRQoL in pediatrics was confirmed, and a strong correlation between disease severity scores and HRQoL in children with psoriasis was found in this study. Taking HRQoL indices into account while managing adolescent patients will improve our insight into the patient's experience and may provide better patient adherence to treatment.

Efficacy of narrowband UVB phototherapy in early-stage mycosis fungoides in Iranian patients.

Narrowband UVB (NB-UVB) has been shown to be effective for the treatment of early mycosis fungoides (MF) in light-skinned patients, but the effect of NB-UVB on patients with darker skin phototypes needs further investigation. The aim of this study was to evaluate the effect of NB-UVB in the treatment of early-stage MF in Iranian patients. In this retrospective study, 24 patients with the diagnosis of early MF (9 stage AI, 15 stage IB) were enrolled. All patients were treated with NB-UVB phototherapy 2-3 times weekly. After achieving complete response, a maintenance treatment was recommended. The response rate, side effects, and recurrence rate in the follow-up period were assessed. The follow-up period was ranged 6 to 24 months. Ten patients (41.7%) had complete remission after a mean number of 42.9 treatment and mean cumulative dose of 58.11 J/cm2. Twelve patients (50%) had partial response, and 2 patients (8.3%) had no response. After discontinuation of maintenance treatment, 4 of 10 patients (40%) with complete remission relapsed within a mean of 5 months. Side effects were limited to erythema (12.5%) and hyperpigmentation (4%). NB-UVB is a safe and effective method for the treatment of early MF, but it seems that more treatment sessions and higher doses of NB-UVB are required for darker skin phototypes.

Dermatological manifestations associated with COVID-19: A comprehensive review of the current knowledge.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has become a significant health problem globally. The virus has spread widely and become a global pandemic. The pathophysiology for SARS-CoV-2 has not been explained clearly. It has been associated with several multiorgan symptoms, among which its dermatological manifestations are of great interest. Primarily, there has been no report of skin features among COVID-19 patients. Nevertheless, recently there have been several reports regarding COVID-19 patients who presented with cutaneous manifestations. In the current review, we focus on the various cutaneous manifestations of COVID-19 infection.

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.