Mucocutaneous Disorder Research Articles

Pemphigus and mucous membrane pemphigoid: An update from diagnosis to therapy.

Pemphigus diseases (PDs) and mucous membrane pemphigoid (MMP) are a group of immune-mediated mucocutaneous disorders clinically characterized by the formation of blisters, erosions and ulcers. The skin and mucous membranes are predominantly affected, with the oropharyngeal mucosa as the initially involved site. Ocular involvement is also a frequent feature of these diseases. Because of the considerable overlap in their clinical presentations, the diagnosis of PDs vs. MMP can be challenging. A recognition of their specific immunological and histopathologic features is crucial in the differential diagnosis. Treatment modalities include systemically administered corticosteroids, steroid-sparing immunosuppressive agents, and biologic therapies (rituximab, intravenous immunoglobulins, and anti-tumor necrosis factor agents). Topical, oral, conjunctival, or intralesional corticosteroids as well as anti-inflammatory drugs and antibiotics are prescribed as needed.

Expression of Cluster of Differentiation 1a-Positive Langerhans Cells in Oral Lichen Planus.

Background/Purpose:Lichen planus is a T-cell-mediated mucocutaneous disorder characterized histopathologically by a band of chronic inflammatory cells in the subepithelial zone and degeneration of basal layer. The present study was aimed to evaluate the distribution and quantitative assessment of cluster of differentiation 1a (CD1a)-positive Langerhans cells (LCs) in oral lichen planus (OLP), thus to determine the role of LCs pertaining to the changes occurring in OLP.Materials and Methods:Five cases of normal oral mucosa and 20 cases of OLP were immunostained with CD1a antibody; the positive cells were counted manually in the photomicrographs and statistically analyzed using t-test, Mann–Whitney test, and Wilcoxon signed-rank test.Results:The average percentage of CD1a-positive LCs in normal subjects was 0.9%, and in the OLP cases higher percentage was observed (3.93%). The statistical comparison of these two parameters was significant (P=0.018). The degree of basal cell degeneration and density of subepithelial infiltrate on statistical comparison with the concentration of CD1a-positive LCs showed significant results.Conclusion:LCs play a pivotal role in the recruitment of CD4+ and CD8+ cells to the subepithelial region and basal keratinocytes apoptosis. A small number of study subjects, assessment of only CD1a molecule and LCs in the epidermis only were a few of the drawbacks of the study.

Third dimension on histopathological aspect of oral lichen planus: An innovation in teaching oral pathology

Oral lichen planus is a chronic mucocutaneous disorder. There are plethora of 2D histopathological images, but 3D images and 3D animation video of the same have not been published so far. Therefore, this article is a preliminary attempt to present the same which the author has designed herself.

Chronic Inflammatory Mediators Induced Malignant Changes in Inflammatory Microenvironment of Oral Potentialy Malignant Conditions - An Emerging Concept

Potentially malignant conditions of the oral cavity are potential threat to mankind because of its malignant changes later. Oral potentially malignant conditions are chronic inflammatory mucocutaneous disorder affecting oral mucosa. Inflammatory mediators induced by chronic inflammatory microenvironment of premalignant conditions are cytokines, chemokines, growth factors, proteolytic enzymes, released by inflammatory cells such as macrophages, lymphocytes, neutrophils, mast cells, activate transcriptional factors such as NF-kB, STAT-3 and HIF-1, promotes cell proliferation, angiogenesis, tumor promotion, resistant to apoptosis, epithelial to mesenchymal transition, induced invasion and metastasis. Carcinoma associated fibroblasts in tumor microenvironment originated by activated fibroblasts secretes cytokines and growth factors promotes tumor progression by cell proliferation, angiogenesis, cell survival, genomic instability, invasion and metastasis. Myeloid derived suppressor cells are specialized heterogeneous immature myeloid progenitor cells that are dendritic cells, macrophages, granulocytes produced upon chronic inflammatory mediators. These cells responsible for immune evasion, immunosuppression and tumor progression by various mechanisms and interaction with other immune cells, activating transcriptional factors such as NF-kB and STAT-3. This article describe about roles of chronic inflammatory cells and their mediators in inflammatory microenvironment of premalignant conditions bring about malignant changes in oral sub mucous fibrosis and oral lichen planus.

Topical hyaluronic acid in the management of oral lichen planus: A comparative study.

Oral lichen planus (OLP) is a chronic mucocutaneous disorder seen in clinical dental practice. Despite the progress in research and advances in knowledge, the successful management of OLP is still difficult to achieve. The aim of the present study was to compare the therapeutic effects of triamcinolone (TA) preparation (0.1%) with hyaluronic acid (HA) preparation (0.2%) in the management of OLP. In total, 40 patients of any age or sex who had symptomatic OLP were selected and randomly divided into two groups. Group I received topical 0.1% TA, and group II received topical 0.2% HA preparation three times per day for a period of 4weeks. Basement data were recorded for each patient. Patients were evaluated on days 14 and 21, and after completing the course of treatment. The visual analog scale (VAS) was used for evaluating pain and burning sensation, along with an evaluation of the degree of erythema and mean area of the lesion. Data were analyzed by SPSS 17.0 software using Mann-Whitney and t test. P≤0.05 was considered statistically significant. Our results showed considerable improvement in all of the parameters evaluated. Baseline characteristics, including pain score, size, and clinical characteristics of the lesions, were not different between the two treatment groups. Both TA and HA were found to reduce the VAS score, the degree of erythema, and size of the lesions after treatment. The application of HA is suggested, and is an effective substitute for TA in the treatment of OLP.

Clinical evaluation of photodynamic therapy for the treatment of refractory oral Lichen planus – A case series

Oral lichen planus (OLP) is a chronic inflammatory, immune mediated mucocutaneous disorder of uncertain etiology. Psychologic stress has been found to be a main contributing factor in onset and progression of lesions. Most erosive OLP patients are refractory to available therapies, even corticosteroids, and report remarkable side effects. As photodynamic therapy (PDT) has proved it to be an effective and safe alternative treatment of abnormal or neoplastic cells we employed PDT for this diagnosis. Due to limited literature on application of this method for treatment of refractory erosive OLP, we present a series of 10 cases of bilateral erosive LP treated by 5 -Aminolevulinic acid mediated PDT. Outcome of our clinical cases showed remarkable improvement in lesions with reduction in Reticulation, Erythema, Ulceration (REU) score (from 5 to 3) and burning sensation as recorded by Visual Analogue Scale (Pretreatment VAS ranged from 5 to 8, posttreatment VAS was 0-1). PDT could be used as a complementary treatment method for symptomatic resistant OLP lesions, although our findings necessitate further research to validate the efficacy of this method for control of resistant oral lichen planus.

Methotrexate-Induced Oral Erythema Multiforme: a Case Report

Erythema multiforme (EM) is an inflammatory mucocutaneous disorder. It can be triggered by herpes simplex virus infection or adverse drug reaction. Oral EM is characterized by oral mucosal ulcerations and lip lesions without any skin lesions. A 65-year-old man was referred for painful ulcerations covered with necrotic tissue on the vermillion of the upper and lower lips, lateral border of the tongue, and buccal mucosa. Medical history revealed methotrexate treatment for rheumatoid arthritis. Histopathologic analysis showed ulceration areas and moderate to dense perivascular, mainly lymphocytic inflammatory infiltrate. The sudden onset of extensive ulcerations in the oral cavity, a positive drug history, and histopathologic analysis led to the diagnosis of oral EM. Although oral EM is confined to the oral cavity, subsequent attacks can produce more severe forms of EM. Hence, it is important to identify oral EM for early diagnosis, adequate treatment, and follow-up.

Desquamative Gingivitis: A Sign of Mucocutaneous Disorder

Desquamative gingivitis is characterized by erythematous gingiva, desquamation and erosion of the gingival epithelium.It is a clinical manifestation of various disorders that can manifest as a desquamative lesion of gingiva rather than a disease entity.It is seen mainly in adults, especially women, although rare cases have been observed in children. Failure to evaluate properly and systematically a patient with a clinical condition consistent with desquamative gingivitis can lead to unpleasant outcomes. Clinical features may be symptomatic to asymptomatic with complaints ranging from burning sensation to intense pain.Lesions are found in skin, genitalia, or oral mucosa, although confined to gingiva alone in some patients.Diagnosis and treatment planning depends on history,clinical features,histopathology and immunofluorescence. Correct diagnosis of mucocutaneous disorders where DG is a presenting manifestation involves taking a careful history and thorough intra-oral examination. A definitive diagnosis depends on taking an incisional biopsy from perilesional site and sending a fresh specimen for immunostaining.

Anesthetic management with subcostal transversus abdominis plane block in recessive dystrophic epidermolysis bullosa for peritoneal dialysis catheter replacement: a case report

BackgroundRecessive dystrophic epidermolysis bullosa (RDEB) is a rare, hereditary mucocutaneous disorder that can involve renal insufficiency. If a vascular access for hemodialysis is unavailable, peritoneal dialysis can be utilized. This report describes an anesthetic management with ultrasound-guided transversus abdominis plane block (TAPB) in a patient with RDEB for peritoneal dialysis catheter replacement.Case presentationA 49-year-old woman with RDEB needed to undergo peritoneal dialysis catheter replacement. As general, neuraxial and local infiltration anesthesia can lead to serious complications; we planned anesthetic management with subcostal TAPB as the primary analgesia modality. In the operating theater, surgery was initiated after performing left-sided subcostal TAPB. The patient complained of moderate pain at some points during surgery, and the pain was controlled with intravenous or local anesthetics without serious complications.ConclusionsIn summary, subcostal TAPB could be a useful option for peritoneal dialysis catheter surgery in patients with RDEB.

Identifying Children with HEreditary Coagulation disorders (iCHEC): a protocol for a prospective cohort study

IntroductionIt is challenging to obtain a reliable bleeding history in children who are referred for a suspected inherited bleeding disorder. Bleeding symptoms may be subtle as children face fewer haemostatic...

Drug Delivery Tailored for the Need– Case Series of Oral Lichen Planus

: Lichen planus is an inflammatory mucocutaneous disorder. The pathogenesis of lichen planus is predominantly T cell mediated. The condition is associated with it are hepatitis C, graft versus host disease, medications , dental materials etc. Immune modulators have been widely used in the management of lichen planus. Corticosteroids are the most widely used among them. There is various mode of delivering corticosteroids in oral lichen planus. The systemic administration is reported to cause more adverse drug reaction when compared to local drug delivery systems. The case series describes three cases of lichen planus at different sites. It also high lights the site-specific treatment applied in them.Key words: Lichen planus, Local drug delivery, Corticosteroids, Systemic steroids.

Desmopressin stimulation testing: Response to intravenous and intranasal forms.

Desmopressin is commonly used to reduce bleeding in patients with mucocutaneous bleeding disorders and is available in both intravenous and intranasal forms. Given the variability in response to desmopressin at an individual level, its effectiveness should be assessed with a test dose prior to being advised for use. At this time, no trial has extensively compared the use of intranasal desmopressin to intravenous desmopressin. To determine whether both forms of desmopressin are equally effective in yielding a positive response in laboratory assays in paediatric patients with von Willebrand disease or probable von Willebrand disease. We evaluated medical record data for 58 patients who underwent desmopressin stimulation testing in our haematology clinic during a 1-year period. Data were collected on demographic information and haematologic laboratory assays prior to desmopressin administration and one hour following desmopressin. There was an absolute increase in von Willebrand antigen to levels appropriate for haemostasis following both forms of desmopressin, although this increase was significantly greater in the intravenous group compared to the intranasal group. There was also a significant absolute increase in Ristocetin Cofactor and Factor VIII levels following desmopressin in both groups. Both intravenous and intranasal forms of desmopressin produce a positive response during desmopressin stimulation testing and can be used to identify patients for whom this medication would be effective.

Erythema Multiforme: A Recent Update

Erythema multiforme (EM) is an acute, self-healing inflammatory mucocutaneous disorder which presents with diverse spectrum of cutaneous lesions, hence termed “multiforme”. Oral lesions are quite characteristic and manifest as rapidly rupturing vesicles & bullae forming ill-defined erosions and hemorrhagic encrusted lip lesions. Wide variety of triggering factors for EM have been documented in the literature, but history of prior herpes simplex virus (HS) infection is most widely accepted. Most other cases are seen after the intake of certain medications. EM has been chiefly divided into two main forms- EM minor and EM major. Steven Johnson syndrome & Toxic epidermal necrolysis (Lyell’s disease) are now considered as distinct clinical entities. EM has a self-limiting course and the lesions usually resolve within few weeks. Symptomatic management along with recognition and alteration of the alleged precipitating factors is usually sufficient in the majority of cases. However, in advanced lesions, steroid therapy may be helpful. This paper aims to present a recent update on Erythema Multiforme taking into account its etiopathogenesis, clinical and oral features, diagnostic aids and treatment protocols.

Assessment of Serum Level of Squamous Cell Carcinoma Antigen II in Patients with Lichen Planus

Lichen planus (LP) is a chronic mucocutaneous autoimmune inflammatory disorder of the stratified squamous epitheliumthat mostly affects middle-aged adults. No significant differences in the incidence for LP are noticed between male and femalepatients. Squamous cell carcinoma antigen (SCCA) is known as a tumor biomarker for various squamous cell tumors. It was firstidentified in the uterine cervix by Kato and Torigoe. Total SCCA comprises nearly identical proteins. Both SCCAI and II belongto the ovalbumin-serpin proteinase inhibitor family. The aim of this work was to assess the serum levels of SCCAII in patientswith LP and compare it to its level in normal group. This was a case-control study conducted over a period of six months fromSeptember 2018 to march 2019 included 100 participants, 80 patients suffering from LP. In addition to 20 apparently healthy.Patients were selected from the outpatient clinic of Dermatology and Andrology Department of Benha University Hospitals andKafr Shokr central hospital. We found that Serum levels of SCCAII were significantly higher in patients with LP compared tohealthy control subjects. In conclusion, significant elevation of SSCCAII is associated with LP. Serum SCCAII may become anovel and useful biomarker for evaluating disease activity.

Clinical value of multiplex immune assay of antinuclear antibodies in systemic lupus erythematosus.

A promising trend in the diagnosis of systemic autoimmune diseases is the multiplex immune assay (MIA) of autoantibodies and other laboratory biomarkers using microchips. The aim of the work was to study the diagnostic and prognostic significance of MIA antinuclear antibody (ANA) profiles in systemic lupus erythematosus (SLE). 94 patients with SLE, 70 patients with other rheumatic diseases and 30 healthy donors were examined. ANA (antibodies to doublestranded - dsDNA, Sm, SS-A/Ro, SS-B/La antigens, nucleosomes, ribosomal protein P-RibP and ribonucleoprotein - RNP-70) were determined in the serum by MIA using the xMAP technology. In MIA, antibodies to dsDNA, Sm and RibP have a high diagnostic specificity (Sp) (95.0-99.0%) and a likelihood ratio of positive results (LR+) (9.67-15.0), i.e. are the most "useful" diagnostic tests, and antibodies to RNP-70, SS-A/Ro and nucleosomes are classified as "useful" tests for the diagnosis of SLE (Sp: 84.0-95.0%, LR+> 2.0). Determination of profiles from 3 or more antigen-specific ANA by MIA increases the Sp method to 98.0-100%, and the LR+ - to the maximum values. Profiles from 7 subpopulations of ANA (antibodies to dsDNA, Sm, RibP, SS-A/Ro,SS-B/La, nucleosomes and RNP-70, 57.9%, 71.9%, 82.5%, 61.4 %, 84.2%, 50.9%, 84.2%) were found in the chronic variant of SLE. In the acute course of the disease, 4 subpopulations of ANA are simultaneously detected (antibodies to dsDNA, Sm, SS-A/Ro and nucleosomes, 77.3%, 45.5%, 40.9% and 72.7%); in subacute course there are 2 subpopulations of ANA (antibodies to dsDNA and nucleosomes, 53.3% and 46.7%). The activity index of SLEDAI-2K positively correlates with the concentration of antibodies to dsDNA (r = 0.55, p < 0.05), nucleosomes (r = 0.65, p < 0.05), RibP (r = 0.32; p < 0.05) and Sm (r = 0.36, p < 0.05) in the blood. There was no reliable relationship between the production of varieties of ANA and the index of organ damage. Mucocutaneous disorders, lupus-nephritis and neurolupus were most often associated with the detection of antibodies to dsDNA (53.2-64.0%), nucleosomes (55.3-66.0%), SS-A/Ro (38.0-40.4%) and Sm (27.8-36.2%). MIA of ANA profiles is an important tool for implementing a personalized approach to diagnosis, evaluation of activity, course and clinical and immunologic subtypes of SLE.

English

Mucocutaneous disorders often seen in HIV patients with varying morbidity. The HIV progression is characterized by the declining of CD4 cell counts and emergence of mucocutaneous manifestations. The aim of the study was to evaluate the relationship between CD4 cell counts with mucocutaneous manifestations in HIV patients. This was a cross-sectional study based on medical records at Dr. Sardjito General Hospital during the period January 2011-December 2015. Data of patient’s age, sex, risk factors of transmission, most mucocutaneous manifestations and CD4 cell count were gathered. The correlation between CD4 cell counts with muscocutaneous manifestations were analyzed using chi-square test. A total 928 patients were involved in the study. More than half of the patients were male (65.4%) and mostly, the patients aged 20-29 years (38.69%). The main risk factors for HIV transmission were unsafe sex (75%). The highest CD4 cell counts was 1094 cells/mm3 and the lowest was 1 cell/mm3. We found 306 cases of mucocutaneous manifestations. The most mucocutaneous manifestations was a fungal infection (40.4%) with the highest infection type was oral candidiasis(33.8%); then noninfection (28%) with the highest type was drug eruption(35.9%); and tumors(0.5%) that was only Kaposi sarcoma cases. We also found sexually transmitted infections (STIs) (18.85%) with the highest cases was condyloma acuminata (49.3%). Statistical analysis showed a significantly relationship between CD4 cell counts with a fungal infection (p 200 cells/mm3) increases the risk of viral infection by about 2.5 times and parasitic infections as much as 5 times.

Nikolsky's sign - A clinical method to evaluate damage at epidermal-dermal junction

Soft tissues of the oral cavity are often affected by various mucocutaneous disorders of variable etiology, affecting both the skin and mucosae, with severe clinical manifestations such as blisters involving the tissues; and therefore their appropriate management relies on their correct diagnosis. Clinical signs to elicit characteristics of blisters are a crucial part of the examination of patients with such disorders. It is therefore essential for clinicians to be familiar with, or rather be expert at eliciting these signs to frame an accurate diagnosis, since proper treatment and follow-up will depend on which disease is involved. The Nikolsky's sign is one such sign that can be helpful in the clinical diagnosis of pemphigus group of disease and differentiating it from other blistering dermatoses. This review gives an overview of sign of Nikolsky and other related sign, its clinical presentation and their diagnostic implications, using PubMed and Medline databases searching for articles written in English. Peer-reviewed articles were targeted using the keywords “Nikolsky's sign”, “mucocutaneous disorders” and “pemphigus”. Available full-text articles were read, and related articles were also scrutinized and finally the search was subsequently refined to articles concerning to “Nikolsky's sign”. It was concluded that early recognition of these signs are necessary to prevent delayed diagnosis and for early institution of appropriate treatment of these potentially serious mucosal and dermatological diseases.

Evaluation of a microfluidic flow assay to screen for von Willebrand disease and low von Willebrand factor levels

Background von Willebrand disease (VWD) is a mucocutaneous bleeding disorder with a reported prevalence of 1 in 10 000. von Willebrand factor (VWF) function and platelet adhesion are regulated by hemodynamic forces that are not integrated into most current clinical assays. Objective We evaluated whether a custom microfluidic flow assay (MFA) can screen for deficiencies in VWF in patients presenting with mucocutaneous bleeding. Methods Whole blood from individuals with mucocutaneous bleeding was assayed in a custom MFA. Results Thirty-two patients with type 1 VWD (10/32) or reported mucocutaneous bleeding were enrolled. The platelet adhesion velocity (r = 0.5978 for 750 s-1 and 0.6895 for 1500 s-1 ) and the maximum platelet surface area coverage (r = 0.5719 for 750 s-1 and 0.6633 for 1500 s-1 ) in the MFA correlated with VWF levels. Furthermore, the platelet adhesion velocity at 750 s-1 (type 1 VWD, mean 0.0009761, 95% confidence interval [CI] 0.0003404-0.001612; control, mean 0.003587, 95% CI 0.002455-0.004719) and at 1500 s-1 (type 1 VWD, mean 0.0003585, 95% CI 0.00003914-0.0006778; control, mean 0.003132, 95% CI 0.001565-0.004699) differentiated type 1 VWD from controls. Maximum platelet surface area coverage at 750 s-1 (type 1 VWD, mean 0.1831, 95% CI 0.03816-0.3281; control, mean 0.6755, 95% CI 0.471-0.88) and at 1500 s-1 (type 1 VWD, mean 0.07873, 95% CI 0.01689-0.1406; control, mean 0.6432, 95% CI 0.3607-0.9257) also differentiated type 1 VWD from controls. We also observed an improvement in platelet accumulation after 1-desamino-8-d-arginine vasopressin (DDAVP) treatment at 1500 s-1 (pre-DDAVP, mean 0.4784, 95% CI 0.1777-0.7791; post-DDAVP, mean 0.8444, 95% CI 0.7162-0.9726). Conclusions These data suggest that this approach can be used as a screening tool for VWD.

Coexistence of genital lichen sclerosus and genital warts

Lichen sclerosus (LS) is a chronic, inflammatory, mucocutaneous disorder of the genital and extragenital skin. Anogenital warts are benign proliferative lesions caused by human papillomavirus (HPV), which is found in > 95% of lesions. We present two cases of the coexistence of LS and genital warts: one patient with and one without a previous history of genital warts. According to our knowledge and a literature search, only a few cases of the coexistence of LS and genital warts have been reported.

Oral pigmentations in Laugier-Hunziker syndrome: a case report and review of diagnostic criteria

ABSTRACT Laugier-Hunziker syndrome (LHS) is a rare mucocutaneous disorder, of unknown etiology, characterized by multiple hyperpigmented macules, dispersed mostly on the oral mucosa, occasionally associated with longitudinal ridging of the nails. The diagnosis requires exclusion of other conditions, such as Addison's disease and Peutz-Jeghers syndrome. We report a case of a 34-year-old male patient, presenting with hyperpigmented macules on the lips, buccal mucosa and palate, as well as mild dark striations on toenails. After careful clinical and laboratorial investigations, the diagnosis of LHS was established. Given the lack of aesthetic complaints and symptoms, no treatment was necessary.