JAK Inhibitors in Cutaneous T-Cell Lymphoma: Friend or Foe? A Systematic Review of the Published Literature.

Cutaneous T-cell lymphomas (CTCLs) are a group of lymphoid neoplasms with high relapse rates and no curative treatment other than allogeneic stem cell transplantation (allo-SCT). CTCL is significantly influenced by disruption of JAK/STAT signaling. Therefore, Janus kinase (JAK) inhibitors may be promising for CTCL treatment. This study is a systematic review aiming to investigate the role of JAK inhibitors in the treatment of CTCL, including their efficacy and safety. Out of 438 initially searched articles, we present 13 eligible ones. The overall response rate (ORR) in the treatment with JAK inhibitors in clinical trials was 11-35%, although different subtypes of CTCL showed different ORRs. Mycosis fungoides showed an ORR of 14-45%, while subcutaneous-panniculitis-like T-cell lymphoma (SPTCL) displayed an ORR ranging from 75% to 100%. Five cases were reported having a relapse/incident of CTCL after using JAK inhibitors; of these, three cases were de novo CTCLs in patients under treatment with a JAK inhibitor due to refractory arthritis, and two cases were relapsed disease after graft-versus-host disease treatment following allo-SCT. In conclusion, using JAK inhibitors for CTCL treatment seems promising with acceptable side effects, especially in patients with SPTCL. Some biomarkers, like pS6, showed an association with better responses. Caution should be taken when treating patients with an underlying autoimmune disease and prior immunosuppression.

Clinicopathological Survey of 204 Rosacea Patients Regarding Rosacea Subgroups and Severity.

INTRODUCTION: Few studies have evaluated the histopathological characteristics of clinical rosacea subtypes in detail. OBJECTIVES: To assess rosacea histopathological features in correspondence to clinical subgroups. METHODS: The histopathological findings of 204 rosacea patients were analyzed retrospectively and were compared among clinical subtypes. RESULTS: Thirt-Two Percent of patients were male and 68% were female. Seventy-three patients had erythematotelangiectatic rosacea (ETR) and 110 had papulopustular rosacea (PPR), 12 were ETR + PPR, 4 ocular, 2 phymatous, and 3 had Morbihan's edema. Perivascular and perifollicular lymphohistiocytic infiltration, perifollicular exocytosis, follicular spongiosis, and ectatic vessels were almost found in all subtypes. Solar elastosis was higher in ETR. Spongiosis, exocytosis of inflammatory cells into epidermis, acanthosis, and granulomatous reaction were higher in PPR. Inflammatory cells exocytosis was more in PPR and phymatous. Demodex folliculorum was identified in 27% of ETR, 33.6% of PPR, 50% of phymatous, one ocular patient, and none of Morbihan edema. Demodex brevis were found in 5% of ETR, 3% of PPR, and 50% of phymatous. Demodex brevis not folliculorum was more in phymatous. Spongiosis was the most common finding in ocular rosacea. CONCLUSIONS: Spongiosis, exocytosis of inflammatory cells, and granulomatous reactions were more in PPR. Solar elastosis was more in ETR. Histopathological findings were compatible with clinical subgroups.

Comparing the efficacy of plasma exeresis and cryotherapy for the treatment of seborrheic keratosis: A randomized controlled trial.

BACKGROUND: Seborrheic keratoses (SK) is a benign epithelial skin tumor and plasma exeresis is a new technique. AIMS: To compare the efficacy and safety of plasma exeresis and cryotherapy for treating SK. METHODS: This study is a randomized controlled trial (RCT). One side of each patient was randomly treated with plasma exeresis (peak-to-peak voltage of 3.44 kV and a frequency of 62.5 kHz) and the other side with cryotherapy. RESULTS: Thirty-five males were enrolled. At week 3, 37.1 % (N = 13) of lesions treated by plasma exeresis were clear, which was higher than those treated by cryotherapy 17.1% (N = 6). However, this difference was not significant (p-value: 0.06). At week 6, 16 (57.1 %) out of 28 remaining lesions, treated by plasma exeresis were clear, which was significantly higher (p-value: 0.005) than those completely cleared by cryotherapy in 6 out of 29 remaining lesions (20.7%). The mean physician assessment scale score was significantly reduced in both groups in the second follow-up (plasma group first follow-up 0.91 ± 0.89 vs. second follow-up 0.5 ± 0.64 and p-value: 0.0031; cryo group first follow-up 1.4 ± 0.84 vs. second follow-up 1.1 ± 0.72 and p-value: 0.0002). Regarding side effects, no significant difference was seen (p = 0.438). The most common complications in the plasma and cryotherapy groups were erythema (10/19, 52.63%) and hypo pigmentation (5/13, 38.46%). CONCLUSIONS: Both cryotherapy and plasma exeresis are effective. We observed a significantly higher cleared lesions treated with plasma exeresis in 6 weeks and after two sessions.

Role of imaging in morphea assessment: A review of the literature.

BACKGROUND: Localized scleroderma, known as morphea, is a connective tissue disorder characterized by inflammation and fibrosis of the skin and the soft tissue. There exist no universally accepted validated outcome measures in order to monitor the disease activity. Besides clinical scores to evaluate outcome measures, imaging modalities are increasingly utilized in assessing patients with morphea, such as high-frequency ultrasonography (US), shear-wave elastography (SWE), and magnetic resonance imaging (MRI). However, the accuracy of these imaging modalities in monitoring morphea activity is not yet clear. AIMS: To review the literature regarding the role of imaging modalities in assessing patients with morphea. MATERIALS & METHODS: In this study, we searched the PubMed/Medline database for articles published from inception until February 2023. RESULTS: A total number of 23 original articles in three categories of US, elastography, and MRI were included. DISCUSSION: Regarding US, criteria, including increased dermal thickness, increased echogenicity of the subcutaneous tissue, and decreased dermal echogenicity, were indicators of active morphea lesions when using high frequencies probe (18-20 MHz) color Doppler sonography. Moreover, studies evaluating SWE, a novel method to quantitatively assess tissue stiffness, demonstrated increased dermal stiffness in active lesions. CONCLUSION: Studies showed that MRI can help to determine the depth of disease, particularly as a first-line and follow-up diagnostic tool, especially in generalized and deep morphea. In addition, brain MRI may be useful for patients with localized craniofacial scleroderma experiencing new or worsening neurological symptoms.

A case of acute generalized exanthematous pustulosis following COVID-19 infection and remdesivir.

We report a challenging AGEP case following COVID-19 infection and a history of remdesivir use. Our study highlights the importance of considering history of COVID-19 and remdesivir as possible causative factors when visiting new-onset AGEP patients.

A systematic review of the comparison between needling (RF-needling, meso-needling, and micro-needling) and ablative fractional lasers (CO2, erbium YAG) in the treatment of atrophic and hypertrophic scars.

The aim of this study is to compare needling (RF-needling, meso-needling, micro-needling) and ablative fractional lasers (CO2, erbium-YAG) in the treatment of atrophic and hypertrophic scars in a systematic review. The database was searched, and 10 articles were selected that were relevant in terms of content, topic, and purpose and met the inclusion criteria. Of all the articles reviewed in this study, there were 2 randomized split-face trials (20%), 1 controlled nonrandomized trial (10%), 1 controlled randomized phase III clinical trial (10%), 1 prospective trial (10%), 1 prospective nonrandomized open-label trial (10%), and 1 randomized comparative trial (10%), with the type of study not reported in 3 articles. We used Endnote X8 to review the articles and extract data. After review, the studies were analyzed and categorized. No statistically significant difference was found between the two methods, laser and micro-needling, in the treatment of atrophic and hypertrophic scars in 60% of the articles studied, and both showed significant improvement (70% or more improvement to complete response). Significant improvement was noted in 20% of the studies reviewed for the laser and micro-needling treatment methods. The results of this study show that needling and ablative fractional lasers are tolerable and safe procedures with no significant difference in the treatment of skin scars in sixty percent of the studies.

Dermoscopy of cutaneous granulomatous disorders: A study of 107 cases.

BACKGROUND: Cutaneous granulomatous disorders (CGDs) can share some features, but an accurate assessment of various findings and their pattern can be useful in differentiating them. In addition to common dermoscopic findings for CGDs, some peculiar dermoscopic characteristics can be helpful in distinguishing them. OBJECTIVE: Herein, we aimed to evaluate dermoscopic findings in patients with CGDs and determine the dermoscopic criteria that could suggest the type of granulomatous disorder. MATERIAL AND METHODS: A total of 107 cases including 75 (70.09%) males and 32 (29.90%) females with an established diagnosis of cutaneous leishmaniasis (n = 49), cutaneous sarcoidosis (n = 23), granuloma annulare (GA) (n = 18), and tattoo granuloma (n = 17) confirmed by clinical and pathological studies were included. Based on the previous studies available in the literature, we wrote a checklist containing dermoscopic features of CGDs. Afterward, two dermatologists independently reviewed all dermoscopic images for the presence or absence of each item on the checklist. Descriptive analysis, fisher exact, chi-square, and t-test were used. The granulomatous disorders with larger sample sizes were selected for further analysis, including the univariate and conditional multivariate logistic regressions. RESULTS: The most prevalent nonvascular findings in all of our CGD patients were white scaling (N = 67%, 62.61%), diffuse or localized orange structureless areas (N = 53%, 49.53%), and diffuse erythema (N = 48%, 44.85%). Furthermore, the most frequent vascular findings in all of our CGD cases were branching and arborizing vessels (N = 30%, 28.03%), linear irregular (N = 30%, 28.03%), and dotted vessels (N = 27%, 25.23%). CONCLUSION: For differentiating leishmaniasis from sarcoidosis by dermoscopy, white scaling and white scarring areas are more suggestive of cutaneous leishmaniasis, whereas the presence of arborizing vessels would be more in favor of sarcoidosis. When comparing GA to cutaneous leishmaniasis, the latter significantly shows more linear irregular vessels, hairpin vessels, white scaling, and white scarring areas. In the case of differentiating sarcoidosis from GA, the presence of hairpin vessels would be suggestive of sarcoidosis.

A Systematic Review of Histopathologic Surveys on Mucocutaneous Biopsies in Patients Developed COVID-19 Vaccine-Related Dermatologic Manifestations.

ABSTRACT: Coronavirus 2 is an infectious agent primarily identified as the cause of a pandemic viral pneumonia. With the mass vaccination against this virus, one of the health issues is the safety of currently available vaccines considering their adverse reactions. This systematic review was conducted to assess and summarize all reported data on histopathologic findings associated with mucocutaneous reactions that developed after COVID-19 vaccination for a better pathophysiology interpretation and clinical management of these reactions. A systematic search was performed in PubMed, Web of Science, and Scopus databases as well as Google Scholar engine for relevant English articles published till July 1, 2022. This review includes 131 studies with a total number of 287 cases. Eruptions that underwent a biopsy were mostly described as erythematous maculopapular, papulosquamous, vasculitis-like, lichenoid, or urticarial lesions. Histopathology revealed spongiosis, interstitial, and perivascular lymphohistiocytic infiltration, erythrocyte extravasation, parakeratosis, endothelial inflammation, and the like. Findings were highly consistent with morbilliform erythema, psoriasiform dermatosis, leukocytoclastic vasculitis, and lichenoid or urticarial drug reactions. The majority of these reactions had a mild nature and were primarily observed in patients with underlying health conditions. Microscopic evaluation was also consistent with transient inflammatory changes, and features like neutrophilic infiltrates, subcorneal pustules, and vasculopathy were less frequently reported than what seen in COVID infection. Therefore, dermatologic reactions developing after vaccination in the general population should not hinder a complete vaccination.

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.

Multiple dermatofibromas, associated clinical and histological characteristics: A systematic review.

Multiple dermatofibromas (DFs) are rare benign fibrohistiocytic lesions characterized by asymptomatic hyperpigmented nodules. Several diseases, like systemic lupus erythematosus (SLE) and human immunodeficiency virus (HIV) infection, are found to be associated with multiple DFs. Here, we designed a systematic review by an electronic search of PubMed and Embase databases to select case reports of multiple DFs (29 May 2021). From 2,145 initially found articles, 96 studies (106 cases) were included. We classified multiple DFs (>1 DF lesion) into four subtypes and separately investigated clinical characteristics of each one: multiple eruptive DFs (MEDFs) (n = 45), multiple (n = 41), multiple clustered DFs (MCDFs) (n = 18), and giant combined (n = 2). The patients' mean age was 38.3 ± 14.7 years. The majority were female (61.3 %). The lesions were commonly on the trunk and extremities (36.8 %). MEDFs (n = 36) had the most rapid disease onset (2.0 ± 6.6 years). Immunosuppression induced by either HIV (10.3 %) and hematologic malignancy (9.4 %) or immunosuppressive drugs (23.4 %) along with SLE (19.8 %) were the most observed associations. However, 66.7 % of the MCDF patients were otherwise healthy individuals. As for disease management, surgery and follow-up were the preferred options. Most of the cases showed neither resolution nor development of new lesions in follow-up.

Evaluating the Perception of Mycosis Fungoides Patients About Their Disease Before and After Educating Them.

Introduction: Patient-held beliefs are important for disease management and few studies have evaluated illness perception of Mycosis Fungoides (MF) patients. Objectives: Here, we aimed to determine the effect of educating MF patients on their perception of their disease. Methods: Patients with diagnosed MF were asked to fill the Illness Perception Questionnaire-Revised (IPQ-R) once before education and once 3 months later. Results: Fifty-five patients, 41 men and 14 women, with a mean age of 45.5 ± 13.9 years were enrolled. Regarding the main etiologic factor, most patients cited anxiety (91%). After education, the most significant changed belief on disease etiology was immune system dysfunction and the change was twenty-six percent which was observed more in patients with higher educational levels, shorter disease duration, and lower MF stages. Regarding the most prevalent clinical manifestations, most patients mentioned erythema (86%). After education, the greatest change in symptom perception was related to lymphadenopathy (32%) which was significantly associated with less disease duration and those treated with phototherapy. Before education, the mean perception score about the disease chronicity was 23.67 ± 3.549 that increased to 27.71 ± 1.66 (P < 0.001). This change was more observed in men (P = 0.03), those with less disease duration, and those treated with phototherapy. Conclusions: Generally, MF patients hold favorable perspectives about their disease and educating them positively improves their illness perception. Patients with higher educational levels and lower stages of the disease showed more significant changes in various aspects of illness perception. Hence, early education is recommended in patients with lower educational levels.

Topical care in pemphigus wounds: A systematic review of the literature.

Pemphigus is a group of autoimmune blistering diseases. Given the ulcerative nature of the diseases, the full healing of ulcers and erosions might be challenging. The aim of this study was to determine various topical wound care options for pemphigus patients, the advantage of each alternative, and to compare their efficacy, safety, and feasibility. In accordance with PRISMA guideline, we performed a systematic search in PubMed/Medline, web of science, and Scopus databases for articles published from inception until February 2, 2022. Out of 703 initially retrieved articles, 11 full texts were included. Our findings were divided into the following categories: silver-containing dressings, paraffin-embedded tulle nets, topical insulin, EPIFIBROIN 0039, platelet gel, and Biobrane®. The most commonly used topical care in pemphigus patients was silver-containing dressings in six studies. All of the included studies reported acceptable outcomes without any severe adverse effects. Due to the few available studies in this field, a definite suggestion cannot be made. We recommend larger randomized controlled studies to identify the best topical care modality in pemphigus patients.

Recalcitrant giant orf recurrence after amputation: A case report and review of the literature.

Orf is caused by a parapoxvirus. We present a recurrent, giant digital orf case in a female patient with a history of hairy cell leukemia. In spite of shave excision, the lesion progressed and recurred after digital amputation. Treatment with topical imiquimod cream and systemic subcutaneous interferon alfa-2a was successful.

A literature review on Janus kinase (JAK) inhibitors for the treatment of immunobullous disorders.

Janus kinases (JAKs) are a group of intracytoplasmic tyrosine kinase proteins that bind to the cytoplasmic part of the transmembrane cytokine receptors and regulate signaling. The pathophysiology of various autoimmune and autoinflammatory conditions relies on JAK/STAT signaling and therefore, the inhibition of JAK/STAT pathways can be a promising treatment for such diseases, especially inflammatory skin conditions. The current study aimed to evaluate the efficacy of JAK inhibitors in the treatment of immunobullous diseases, including pemphigus, pemphigoid, dermatitis herpetiformis, and epidermolysis bullosa. The databases used to identify the studies were Web of Science, Scopus, and PubMed/Medline for studies published until 2/3/2022. The current review suggests that JAK inhibitors may be revolutionary for the future treatments of dermatologic conditions, especially autoimmune bullous disease. Results also indicated the effectiveness of JAK inhibitors for the treatment of immunobullous diseases.

Cutaneous manifestations following COVID-19 vaccination: A report of 25 cases.

Various adverse effects particularly cutaneous manifestations associated with different COVID-19 vaccines have been observed in practice. The aim of our study was to evaluate all patients who presented to our tertiary center with skin manifestations following COVID-19 vaccines injection from September to December 2021. All patients with skin manifestation within 30 days or less following COVID-19 vaccination were enrolled in our case-series. All cases included in our study were diagnosed based on clinical and/or histopathological evaluation and all other possible differential diagnoses were ruled out. Twenty-five individuals including 16 (64%) males and 9 (36%) females with the mean age of 47 ± 17.62 years (range 18-91) were enrolled in our study. Twenty-two (88%) patients developed lesions after Sinopharm vaccine injection and 3 (12%) cases manifested lesions after the AstraZeneca vaccine. Six (24%) patients developed new-onset lichen planus (LP) and 1 (4%) patient manifested LP flare-up. Two (8%) individuals developed psoriasis and 1 (4%) case showed psoriasis exacerbation. One (4%) patient developed new-onset pemphigus vulgaris (PV) and 1 (4%) case experienced a flare of PV lesions. One (4%) patient manifested pityriasis lichenoides et varioliformis acuta (PLEVA) flare-up. Other new-onset cases were as follows: toxic epidermal necrolysis (TEN) (n = 1, 4%), bullous pemphigoid (BP) (n = 2, 8%), alopecia areata (AA) (n = 2, 8%), pytriasis rosea (n = 1, 4%), herpes zoster (n = 1, 4%), cutaneous small vessel vasculitis (n = 1, 4%), erythema multiform (EM) and urticaria (n = 3, 12%), and morphea (n = 1, 4%). Physicians should be aware of the possible side effects especially cutaneous manifestations associated with COVID-19 vaccines.

Immunologic response, Efficacy, and Safety of Vaccines against COVID-19 Infection in Healthy and immunosuppressed Children and Adolescents Aged 2 - 21 years old: A Systematic Review and Meta-analysis.

Children and adolescents form a large proportion of societies and play an important role in the transmission of COVID-19. On the other hand, their education, mental and physical wellness, and safety are compromised which makes vaccination a crucial step to return to normal life. In the current systematic review, the COVID-19 vaccination was evaluated in a total of 50,148 children and adolescents in 22 published studies and 5,279 participants in two ongoing clinical trials. The study was registered in the PROSPERO with the ID# CRD42022303615. Data were collected about multiple vaccines including BNT162b2 (Pfizer), mRNA-1273 (Moderna), JNJ-78436735 (Johnson and Johnson), CoronaVac (Sinovac), BBIBP-CorV (Sinopharm), adenovirus type-5-vectored vaccine, ZyCov-D, and BBV152 (COVAXIN). The immune response and efficacy of such vaccines were 96% - 100% in healthy children and adolescents and were also acceptable in those with underlying diseases and suppressed immune systems. The current systematic review revealed favorable safety profiles of employed vaccines in children and adolescents; however, adverse reactions such as myocarditis and myopericarditis were reported which were transient and resolved entirely. Consequently, vaccinating children and adolescents aged 2 - 21 years old is beneficial to abort the COVID-19 pandemic. Moreover, the risk-benefit assessments revealed favorable results for vaccinating children and adolescents, especially those with underlying diseases and immunosuppressed conditions, alongside adults to prevent transmission, severe infection, negative outcomes, and new variants formation. Also, according to the meta-analysis, the efficacy and immune response of vaccines after the first and second doses were 91% and 92%, respectively. Meanwhile, overall immune response for all vaccines was 95% and 91% for Pfizer vaccine.

A systematic review on COVID-19 vaccination and cosmetic filler reactions: A focus on case studies and original articles.

BACKGROUND: Tissue fillers are among the most popular cosmetic procedures performed and notably, cases of filler reactions after COVID-19 vaccination have been reported. OBJECTIVE: The objective was to determine the characteristics of patients with filler reaction after COVID-19 vaccination and address several considerations that have to be taken into practice. METHODS: A PRISMA compliant systematic search was conducted in Scopus, Web of Science, and PubMed/MEDLINE databases for articles published from inception up to October 21, 2021. RESULTS: Out of 106 initially retrieved articles, four of them were included in our study, and a total number of 13 cases were analyzed. In this study, we found that all of the patients who developed delayed-type reaction (DTR) following COVID-19 vaccination were middle-aged women without any known history of allergy to foods or drugs. All patients had a history of hyaluronic acid (HA) filler injection in their head and neck and demonstrated symptoms particularly swelling, from <1 day up to 10 days after the first or second doses of vaccines. Lisinopril, hyaluronidase, and corticosteroids seemed to have good results in management. CONCLUSION: Although rare, DTR to fillers after COVID-19 vaccination can happen. Physicians should be aware of the pathogenesis and management of this phenomenon.