The ABO blood group antigens in patients with oral lichenoid reaction.

Evaluating the association of ABO blood group with different delayed hypersensitivity reactions, such as oral lichenoid reaction (OLR), can provide a new perspective for clinical practice. Therefore, this study designed to investigate ABO blood group antigens in OLR patients. In this case-control study, the ABO blood group of 112 OLR patients and 117 individuals without oral lesions were included. Gender, age, characteristics of the lesions, medications and restorative materials recorded. Chi-square test used to compare the frequency of ABO blood groups in OLR patients with controls. The O blood group was significantly higher in OLR patients and all its subtypes. Also, there were significant relation between O blood group, and severity of lesions. The frequency of dysplasia was non-statistically significant higher in OLR patients with O blood group than other blood group. Based on the results of the present study, O blood group was significantly more in patients with lichenoid reaction than control group, and AB blood group was the lowest. Also, O blood group showed a positive association with the more severe form of OLR lesions and frequency of dysplasia.

Narrowband ultraviolet B therapy for refractory immune-related lichenoid dermatitis on PD-1 therapy: a case report.

Treatment with programmed cell death 1 inhibitors is associated with a wide range of cutaneous immune-related adverse events, with lichenoid eruptions representing one of the major cutaneous toxicities. We describe the case of an 81-year-old man with metastatic melanoma treated with pembrolizumab who subsequently developed a delayed-onset generalized lichenoid dermatitis. After failing multiple lines of systemic immunosuppression, narrowband ultraviolet B (NBUVB) phototherapy three times per week for 17 sessions resulted in a significant clinical response in his cutaneous eruption and was well tolerated. NBUVB is a safe, lower-cost modality that induces local, skin-specific immunosuppression without the toxicities of traditional systemic immunosuppressive agents. To date, this is the first report of use of NBUVB in immune-related lichenoid dermatitis resistant to multiple standard therapies.

Oral Hypersensitivity Reactions.

Allergic contact hypersensitivity reactions of the oral mucosa pose a significant medical concern for some patients. Oral hypersensitivity reactions can result from a vast number of allergenic chemicals, but occur commonly from dental materials, flavorings, and preservatives. Clinical presentation is varied and often overlaps with other oral conditions, complicating their diagnosis and management. The most common clinical entities associated with oral hypersensitivity reactions are oral lichenoid reactions and allergic contact cheilitis. In addition to reviewing these conditions and their most common corresponding allergens, this article summarizes the pathogenesis of oral hypersensitivity reactions and addresses patch testing pearls.

Hypertrophic lichenoid dermatitis immune-related adverse event during combined immune checkpoint and exportin inhibitor therapy: A diagnostic pitfall for superficially invasive squamous cell carcinoma.

Immune checkpoint inhibitors (ICIs) for cancer treatment have revolutionized the field of medicine. However, an unintended but frequent consequence of ICI therapy is the development of cutaneous immune-related adverse events (irAEs), such as lichenoid dermatitis irAEs (LD-irAEs). The hypertrophic variant of LD-irAE may be a diagnostic challenge since it can mimic superficially invasive squamous cell carcinoma (SCC). A 79-year-old woman with metastatic melanoma who began treatment with an ICI-pembrolizumab-plus exportin-1 (XPO1) inhibitor presented after 1 month of therapy with symmetrical violaceous papules coalescing into plaques and with two nodules of the bilateral dorsal hands. Biopsy of the nodules revealed an actinic keratosis and atypical epidermal proliferation concerning for SCC. However, in the ensuing 3 weeks, the patient developed multiple new erythematous, violaceous, and scaly macules and papules, some coalescing into plaques on the extremities. Biopsies of these lesions revealed exuberant irregular epidermal hyperplasia with hypermaturation and lichenoid infiltrate concentrated at the base of the elongated, broadened rete ridges, consistent with hypertrophic LD-irAE. Treatment included topical fluocinonide ointment, intralesional triamcinolone injections and oral acitretin. Distinguishing hypertrophic LD-irAE and SCC can be challenging since both entities share histopathologic features; thus, correlation with clinical presentation is essential for diagnosis and optimal patient management.

Survival and prognosis of individuals receiving programmed cell death 1 inhibitor with and without immunologic cutaneous adverse events.

BACKGROUND: The treatment response to new immunotherapy in advanced melanoma patients remains varied between individuals. Immune-related cutaneous side effects might have prognostic value. OBJECTIVE: To determine whether development of ≥1 of the 3 immune-mediated cutaneous events (eczema, lichenoid reaction, or vitiligo-like depigmentation) is associated with improved progression-free survival. METHODS: A cohort study of adults with stage IIIC-IV melanoma treated with pembrolizumab or nivolumab during May 1, 2012-February 1, 2018, at Westmead Hospital, Sydney, Australia. Treatment response was based on iRECIST version 1.1. RESULTS: In total, 82 patients of an average age of 59.9 years were included. Median follow-up was 40.7 months; 33 patients had ≥1 target skin reaction. Skin reactions developed in one-third of individuals by 6 months. At any given time, the instantaneous risk of disease progression and death was lower for individuals who had ≥1 cutaneous adverse event (CAE) develop. Compared with individuals with no CAE, the hazard ratio for disease progression and death for individuals who had ≥1 CAE develop was 0.46 (95% confidence interval 0.23-0.91; P = .025) by the time-dependent Cox proportional hazards model. LIMITATIONS: Single-center study. CONCLUSION: This study demonstrates an association between the development of ≥1 of 3 CAEs and improved progression-free survival in this cohort of patients.

Gene expression profiling of lichenoid dermatitis immune-related adverse event from immune checkpoint inhibitors reveals increased CD14+ and CD16+ monocytes driving an innate immune response.

BACKGROUND: Cancer patients receiving antibodies abrogating immune checkpoint pathways may develop a diverse array of immune-related adverse events (irAEs), of which lichenoid dermatitis (LD) is the most common. The mechanism driving the emergence of these irAEs remain understudied, underscoring a critical need to determine the unique gene expression profiles and immune composition in LD-irAE. METHODS: LD-irAE (n = 3) and benign lichenoid keratosis (BLK) control (n = 3) were profiled with NanoString nCounter PanCancer Immune Profiling Panel interrogating the mRNA levels of 770 genes. Immunohistochemical (IHC) studies (n = 14 samples) for CD14, CD16, T-Bet, Gata-3, and FoxP3 were further evaluated using Aperio digital image analysis. RESULTS: The LD-irAE showed downregulation of 93 mRNA transcripts (P < 0.05) and upregulation of 74 mRNA transcripts (P < 0.04) including toll-like receptor (TLR) 2 and TLR4 (P < 0.05). CD14+ and CD16+ monocytes quantified by IHC (H-score) were higher in LD-irAE than in the BLK control (P < 0.05). The immune composition of LD-irAE exhibited higher numbers of T-Bet+ (Th1) cells compared with Gata-3+ (Th2) cells (P = 0.016) and lower numbers of FoxP3 (T regulatory) cells (P = 0.008). CONCLUSIONS: LD-irAE exhibited activation of CD14/TLR innate immune response with increased CD14+ and CD16+ monocytes compared with BLK control. CD14/TLR signaling may drive the development of LD-irAE.

[Toxidermy mimicking acute chemotherapy-induced lupus erythematosus]. / Une toxidermie mimant un lupus érythémateux aigüe chimio-induit.

Acute chemotherapy-induced lupus erythematosus (ALE) is rare. A few cases have been reported in the literature criminalizing capecitabine, paclitaxel and docetaxel. We report the case of a 64-year old female patient without a history of autoimmune diseases or of drug allergy followed up for invasive ductal carcinoma in the right breast immediately metastatized to the liver and to the lymph nodes. After AC60 first line chemotherapy regimen (a total of 6 cycles), she was treated with docetaxel at a dose of 100 mg/m2. After 5 cycles, she had diffuse erythematous lesions on both hands, forearms, cheeks and on the peribuccal area. She underwent corticosteroid therapy with sun protection and could continue the same chemotherapy until the eighth cycle. Patient's evolution was marked by the progression of the disease. She was treated with capecitabine at a dose of 1250 mg/m2 twice a day. After six cycles she had erythematosquamous and itchy patches on the face resembling the wings of a butterfly (Panel A, Panel B) with oral ulceration and digital pulpitis (Panel C). This initially suggested acute chemotherapy-induced cutaneous lupus erythematosus. Biopsy suggested lichenoid toxidermia. Immunological assessment was performed to exclude chemotherapy-induced cutaneous lupus erythematosus, which showed anti-native DNA antibodies and negative anti-histone antibodies. Anti-nuclear antibody test is positive at 320; this test may be positive in 50-70% of patients with breast cancer, ENT or lymphoma. In the light of these results the diagnosis of toxidermia was the more likely.

Immune response patterns in non-communicable inflammatory skin diseases.

Non-communicable inflammatory skin diseases (ncISD) such as psoriasis or atopic eczema are a major cause of global disease burden. Due to their impact and complexity, ncISD represent a major challenge of modern medicine. Dermatology textbooks describe more than 100 different ncISD based on clinical phenotype and histological architecture. In the last decades, this historical description was complemented by increasing molecular knowledge - and this knowledge is now being translated into specific therapeutics. Combining the enormous advances made in lymphocyte immunology and molecular genetics with clinical and histological phenotyping reveals six immune response patterns of the skin - type I immune cells cause the lichenoid pattern characterized by immune-mediated cell death of keratinocytes; type II immune cells underlie the eczematous pattern with impaired epidermal barrier, infection and eosinophils as well as the bullous pattern with loss of epithelial integrity; Th17 cells and ILC3 mediate the psoriatic pattern characterized by acanthosis, high metabolic activity and neutrophils; dysbalance of regulatory T cells causes either the fibrogenic pattern with rarefication of cells and dermal thickening or the granulomatous pattern defined by formation of granulomas. With more and more specific therapeutic agents approved, classifying ncISD also according to their immune response pattern will become highly relevant. This review defines the six immune response patterns of ncISD and highlights therapeutic strategies targeting key lymphocyte mediators.

Lichenoid drug eruption induced by colchicine: case report.

Lichenoid drug eruption (LDE) is a common cutaneous side effect of drugs including antimalarials, antihypertensives, nonsteroids, anti-inflammatory drugs and diuretics. The physiopathologic relationship between colchicine treatment and LDE is unclear. There is very little documentation of LDE induced by colchicine in the literature. In this report, we present a case that developed LDE on the abdomen and the legs during the colchicine treatment.

Sweat as an Efficient Natural Moisturizer.

Although recent research on the pathogenesis of allergic skin diseases such as atopic dermatitis has focused on defects in skin genes important for maintaining skin barrier function, the fact that excreted sweat has an overwhelmingly great capacity to increase skin surface hydration and contains moisturizing factors has long been ignored: the increase in water loss induced by these gene defects could theoretically be compensated fully by a significant increase in sweating. In this review, the dogma postulating the detrimental role of sweat in these diseases has been challenged on the basis of recent findings on the physiological functions of sweat, newly recognized sweat gland-/duct-related skin diseases, and therapeutic approaches to the management of these diseases. We are now beginning to appreciate that sweat glands/ducts are a sophisticated regulatory system. Furthermore, depending on their anatomical location and the degree of the impairment, this system might have a different function: sweating responses in sweat glands/ducts located at the folds in hairy skin such as on the trunk and extremities could function as natural regulators that maintain skin hydration under quiescent basal conditions, in addition to the better-studied thermoregulatory functions, which can be mainly mediated by those at the ridges. The normal functioning of sweat could be disturbed in various inflammatory skin diseases. Thus, we should recognize sweating disturbance as an etiologic factor in the development of these diseases.

Lichen striatus versus linear lichen planus: a comparison of clinicopathological features, immunoprofile of infiltrated cells, and epidermal proliferation and differentiation.

BACKGROUND: Lichen striatus (LS) and linear lichen planus (LLP) are separate uncommon disorders belonging to linear inflammatory dermatoses. The immunotyping of inflammatory cells has been investigated in LS and lichen planus (LP), but epidermal proliferation and differentiation have little been described in LS and LLP. METHODS: The clinical and pathological data of eight patients with LS and seven with LLP were retrospectively collected. Immunotyping of infiltrated cells and expression of Ki-67, K16, involucrin, and filaggrin were stained by immunohistochemistry in skin lesions of these patients and normal skin of eight healthy controls. RESULTS: Dermal infiltrates contained primarily CD3+ and CD68+ cells in three groups. CD4+ cells were predominantly located in the perivascular area, while CD8+ cells were frequently close to the junctional zone. Compared with control skin, epidermal and dermal CD1a+ cells, and dermal CD3+, CD4+, CD8+, and CD68+ cells were increased in LS and LLP (P < 0.05), while Ki-67+ cells were significantly high in LLP (P < 0.05) but not in LS. K16 and involucrin expression in LLP were more extensive than in LS, and filaggrin expression was similar between both entities. CONCLUSIONS: Our results indicate that the predominance of CD8+ cells and increased epidermal proliferation and abnormal keratinization are present in both dermatoses, although the levels of the above indexes are mild in LS as compared to LLP. These two entities might be due to the interaction of infiltrated cells and keratinocytes, and CD8+ cells could play a pivotal role in their pathogenesis.

Oral lichen planus: an update on its pathogenesis.

Oral lichen planus (OLP) is a common T cell-mediated mucocutaneous disease of unknown etiology. A great number of factors have been suggested as relevant to the etiology of this disease. In this article, the authors assemble recent knowledge about the pathogenesis of OLP, discuss some proposed hypotheses, and compare OLP with oral lichenoid lesions.

Lichenoid reaction as a potential immune response marker of intratreatment histological response during successful vismodegib treatment for a giant basal cell carcinoma.

We report an 83 year-old patient with a 13 × 7.5 cm(2) basal cell carcinoma (BCC) successfully treated with the combination of vismodegib and minimal surgery. On Day 109, a 0.9 cm papule suspicious for residual BCC was seen centrally within a large pink atrophic plaque. This lesion was excised; pathology confirmed BCC with negative surgical margins. Simultaneously, suspecting noncontiguous histologic response, we performed 21 biopsies at the periphery of the pretreatment tumor location. Seventeen (17/21, 81%) revealed lichenoid dermatitis. No tumor was seen on any. We believe the lichenoid dermatitis observed is a novel finding for two reasons. First, it may be considered a marker of a positive intratreatment response. This may help guide clinicians on the optimal treatment duration of vismodegib to maximize efficacy and mitigate side effects. Second, we think it suggests an additional mechanism of vismodegib action, possibly via local immune effects. Further investigations are warranted.

Human T-lymphotropic virus 1 (HTLV-1)-associated lichenoid dermatitis induced by CD8+ T cells in HTLV-1 carrier, HTLV-1-associated myelopathy/tropical spastic paraparesis and adult T-cell leukemia/lymphoma.

Human T-lymphotropic virus type 1 (HTLV-1) induces adult T-cell leukemia/lymphoma (ATLL), HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and carrier. ATLL is a mature CD4+ CD25+ CCR4+ T-cell neoplasm, and approximately half of patients have direct skin involvement manifesting patch, plaque, tumor, multiple papules, erythroderma and purpura. However, there exist secondary eruptions without tumor cell infiltration in patients with ATLL or HAM/TSP and carriers of HTLV-1. To clarify the presence of reactive skin eruptions in HTLV-1-infected individuals, we reviewed our patients with HTLV-1-associated diseases. In 2002-2012, we saw 50 ATLL or HAM/TSP patients and HTLV-1 carriers presenting with skin lesions. We retrospectively selected cases that histologically showed lichenoid tissue reactions with predominant infiltration of CD8+ T cells, but not CD4+ tumor cells. The cases included erythroderma (HTLV-1 carrier), lichen planus (HTLV-1 carrier), alopecia areata (HAM/TSP), chronic actinic dermatitis (HTLV-1 carrier to acute ATLL conversion) and discoid lupus erythematosus (smoldering ATLL). They were graft-versus-host disease-like, major secondary lesions and seen in HTLV-1 carriers and patients with HAM/TSP and smoldering ATLL. We coin the term HTLV-1-associated lichenoid dermatitis (HALD) to encompass the conditions. HALD may occur in association with the elevated immunity toward HTLV-1-infected CD4+ T cells, thus sharing the pathogenetic role of cytotoxic T cells with HAM/TSP.