Lichenoid drug eruption associated with imatinib mesylate therapy.

INTRODUCTION: Imatinib Mesylate (IM), a tyrosine kinase inhibitor, has been reported to cause several adverse reactions, most of them with cutaneous involvement. Non- Lichenoid IM associated skin reactions have been sufficiently- recorded. To our knowledge, Lichenoid Drug Eruption (LDE) is recorded in a minority of registries. CASE REPORT: To describe an LDE induced case by IM treatment. TREATMENT AND OUTCOME: Histological Confirmation and promptly dermatological consultation relieved successfully the cutaneous adverse event. DISCUSSION: Ongoing expansion of IM usage in a wide spectrum of new indications is more likely to make physicians experience such LDE cutaneous side effects more often. Hence, they should be highly suspicious to early detect these distinct histologic entities, handle these undesired complications and guarantee satisfactory immediate outcomes, avoiding frivolous IM dosage modifications.

Erythema ab igne with features resembling keratosis lichenoides chronica.

Erythema ab igne (EAI) is an asymptomatic dermatosis that develops in response to chronic exposure to low-grade heat. Characteristic findings on histopathology include epidermal atrophy, dermal elastosis, atypical histiocytes, and melanin and hemosiderin deposition. Reactive endothelial changes and prominent vascular proliferation are variable. Keratosis lichenoides chronica (KLC) is a rare lichenoid hyperkeratotic dermatosis. Acanthosis with parakeratosis and a lichenoid interface dermatitis with lymphocytes, histiocytes, and plasma cells are characteristic findings of KLC. Although its etiology remains unclear, KLC has been reported to occur in response to heat. Herein, we report a case of EAI with features resembling KLC.

Dermatologic toxicities to immune checkpoint inhibitor therapy: A review of histopathologic features.

Antineoplastic agents that use the immune system have revolutionized cancer treatment. Specifically, implementation of immune checkpoint inhibitors, monoclonal antibodies that block cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein 1, or programmed cell death ligand 1 show improved and sustained responses in patients with cancer. However, these agents are associated with a plethora of adverse events, many manifesting in the skin. As the clinical application of cancer immunotherapies expands, understanding the clinical and histopathologic features of associated cutaneous toxicities becomes increasingly important to dermatologists, oncologists, and pathologists to ensure timely diagnosis and appropriate care. This review discusses cutaneous reactions to immune checkpoint inhibitors, focusing on histopathologic features.

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.

Annular lichenoid dermatitis of youth-Recurrent case of rare skin disease treated with cyclosporine.

Annular lichenoid dermatitis of youth (ALDY), first described in 2003, represents an uncommon entity whose etiopathogenesis is still debated. Futhermore, the optimal treatment for ALDY is yet to be established. We report a 9-year-old girl who presented with annular and oval erythematous lesions mostly on her trunk, with several lesions on the neck, groin, flanks, and upper extremities. The lesions had histological and immunohistochemical features characteristic for ALDY. Treatment with H1-antihistamines, topical corticosteroid, and UVB therapy was unsuccessful, while systemic treatment with cyclosporine induced complete remission.

Lichenoid granulomatous dermatitis revisited: A retrospective case series.

BACKGROUND: Lichenoid granulomatous dermatitis (LGD) is an uncommon reaction pattern for which clinical correlates can be difficult to establish. LGD combines vacuolar degeneration with variable types of granulomas. OBJECTIVE: To determine clinical correlates of LGD. METHODS: The laboratory information systems at the University of Florida, the Medical College of Wisconsin, and Inform Diagnostics Research Institute were queried to identify 56 cases of LGD. Cases were reviewed for information regarding eosinophils, plasma cells, deep perivascular infiltrates, granuloma subtype, parakeratosis, epidermal atrophy, psoriasiform epidermal changes, pseudoepitheliomatous hyperplasia, periadnexal inflammation, vasculitis, and red blood cell extravasation. RESULTS: The most common clinical correlates were drug eruption (39.3%, n = 22) and lichenoid keratosis (19.6%, n = 11). Tattoo reaction, postherpetic dermatitis, and scabies or postscabietic dermatitis each accounted for 7.1% (n = 4) of cases. Pigmented purpuric dermatosis and lichen striatus each accounted for 5.4% (n = 3) of cases. Dermal eosinophils (P = .005) and psoriasiform epidermal changes (P = .055) were associated with drug hypersensitivity. Perineural (P = .049) and perifollicular (P = .003) inflammation were associated with tattoo reaction and postherpetic dermatitis. Red blood cell extravasation was helpful in cases of pigmented purpuric dermatosis (P = .049). LIMITATIONS: This study is limited by its retrospective nature and statistical power. CONCLUSION: Dermal eosinophilia, psoriasiform epidermal changes, periadnexal inflammation, and red blood cell extravasation might aid in the clinical diagnosis of patients with LGD.

Lichenoid dermatitis from immune checkpoint inhibitor therapy: An immune-related adverse event with mycosis-fungoides-like morphologic and molecular features.

Cutaneous immune-related adverse events (irAEs) are a known consequence of immune checkpoint inhibitor (ICI) therapy and may exhibit a spectrum of morphologic features both clinically and histologically. Lichenoid dermatitis associated with ICI therapy (LD-ICI) is the most frequently encountered histopathologic type of irAE biopsied by dermatologists. There is frequent clinical and histologic overlap between irAEs and several reactive and neoplastic dermatologic disorders; thus, clinical information is essential. LD-ICI with histologic, immunohistochemical, and molecular features typical of mycosis fungoides (MF) are unique. Here, we report a patient who developed LD-ICI with MF-like morphologic features with monoclonal T-cell receptor gene rearrangement on consecutive biopsies during ICI therapy. The development of monoclonal LD-ICI is important for clinicians and pathologists to recognize in patients receiving ICI therapy.

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.

[Annular lichenoid dermatitis of youth: A case report and literature review]. / Dermatite lichénoïde annulaire du sujet jeune : un cas et revue de la littérature.

BACKGROUND: Annular lichenoid dermatitis of youth (ALDY) is a rare form of dermatitis mainly affecting children and young people. All cases reported show a consistent clinical and histological picture. This is the first case described in the French literature. PATIENTS AND METHODS: A 5-year-old girl presented an annular isolated patch of the lower abdomen with an erythematosquamous border and central hypopigmentation for one year. Topical corticosteroids and pimecrolimus proved effective but relapse occurred after treatment withdrawal. DISCUSSION: Over sixty cases of ALDY are described in the English-language medical literature. The main differential diagnosis is childhood mycosis fungoides, particularly the hypopigmented variant. Biopsy is necessary for diagnosis since it can reveal typical histological features. Histopathology in all cases shows lichenoid reaction with CD4+ and CD8+ polyclonal lymphocytes. It is limited to the tips of rete ridges and associated with apoptosis of keratinocytes resulting in quadrangular-shaped rete ridges. Our case does not demonstrate either epidermotropism or atypical lymphocytes. CONCLUSION: Annular lichenoid dermatitis of youth (ALDY) is a poorly known distinctive entity within the lichenoid dermatitis family. Clinical-histological correlation is essential to diagnosis. The etiology is still unknown and the course is mostly chronic.

Expanding the clinicopathological spectrum of late cutaneous Lyme borreliosis (acrodermatitis chronica atrophicans [ACA]): A prospective study of 20 culture- and/or polymerase chain reaction (PCR)-documented cases.

BACKGROUND: The diagnosis of acrodermatitis chronica atrophicans (ACA), the late cutaneous manifestation of Lyme borreliosis, can be challenging. Histologic changes in ACA have been described in a few studies from endemic countries, relying on cases documented by serology only. OBJECTIVES: We sought to reassess the clinicopathological spectrum of ACA in a series of thoroughly documented cases. METHODS: Patients prospectively included in a national prospective study were selected on the basis of positive culture and/or polymerase chain reaction of a skin biopsy sample. The diagnosis of ACA was confirmed by reviewing the clinical and serologic data. Histopathological samples were carefully reviewed. RESULTS: Twenty patients were included. Unusual clinical features (ie, numerous small violaceous patches and equidistant small spinous papules with background faint erythema) were observed in 2 patients. Histopathological examination revealed a classic plasma cell-rich perivascular and interstitial pattern with telangiectases in 16 of 25 samples, whereas strikingly prominent granuloma annulare-like or lichenoid features were observed in 4 and 2 of 25 cases, respectively, and discrete nonspecific minor changes in 3 of 25 cases. LIMITATIONS: The small number of patients was a limitation. CONCLUSIONS: Genuine culture- and/or polymerase chain reaction-proven ACA can rarely present as numerous violaceous patches or cluster of spinous papules clinically, and as a granuloma annulare-like or lichenoid dermatosis histologically.

Cutaneous Complications of Targeted Melanoma Therapy.

OPINION STATEMENT: The landscape of advanced and metastatic melanoma therapy has shifted dramatically in recent years. Since 2011, eight drugs (ipilimumab, vemurafenib, dabrafenib, trametinib, cometinib, pembrolizumab, nivolumab, and talimogene laherparepvec) have received FDA approval for the treatment of advanced or metastatic melanoma, including combination regimens of both small molecule kinase and immune checkpoint inhibitors. These therapies have revolutionized the management of unresectable regional nodal and distant melanoma, providing hope of extended survival to patients. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, malignant lesions and more serious or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment in order to improve patient outcome. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining patient quality of life is of paramount importance. Oncologists should be aware of the common cutaneous toxicities associated with these medications and should be encouraged to involve dermatologists in the collaborative care of advanced melanoma patients. Close communication between oncologists and dermatologists can help to avoid unnecessary dose reduction or treatment discontinuation and identify situations when treatment cessation is truly warranted.

Annular Lichenoid Dermatitis of Youth: A Report of 2 Cases and a Review of the Literature. / Dermatitis anular liquenoide de la infancia. Descripción de 2 casos y revisión de la literatura.

Annular lichenoid dermatitis of youth is a lichenoid dermatosis of unknown etiology. It mostly affects children and adolescents and has well-defined clinical and histological characteristics that permit a diagnosis. We present 2 new cases of annular lichenoid dermatitis of youth with classical clinical features in 2 girls, aged 2 and 4 years. The histologic findings, however, differed from those reported in the literature in that the lichenoid inflammatory infiltrate was located primarily at the top of the dermal papillae and not at the tips of the rete ridges. In both cases, the lesions regressed spontaneously without treatment.

Hypertrophic lichen sclerosus sine sclerosis: clues to histopathologic diagnosis when presenting as psoriasiform lichenoid dermatitis.

BACKGROUND: The histopathologic diagnosis of lichen sclerosus (LS) is usually facilitated by a subepidermal zone of sclerosis. In the absence of sclerosis, LS mostly presents itself as a psoriasiform lichenoid dermatitis that may be difficult to distinguish from other diseases. OBJECTIVE: We sought to assess histopathologic findings that allow recognition of LS in the absence of sclerosis. METHODS: We studied 28 criteria in 100 biopsy specimens of LS from genital or perianal skin, including 55 cases with marked sclerosis, 16 cases with mild sclerosis confined to foci of the papillary dermis and 29 cases without sclerosis. Fifteen cases each of the early plaque stage of mycosis fungoides, lichen planus and lichen simplex chronicus were studied for comparison. RESULTS: Some histopathologic hallmarks of LS were seen chiefly in sclerotic lesions and, therefore, did not contribute to the diagnosis of difficult cases, such as dissolution of elastic fibers. Others were seen rarely in non-sclerotic lesions but might be helpful in individual cases, including follicular hyperkeratosis and thickening of the basement membrane. Findings that were more common and may be utilized as clues to the histopathologic diagnosis of non-sclerotic LS include tiny foci of homogenized tissue in dermal papillae, marked fibrosis with thickening of the papillary dermis, marked thickening of individual collagen fibers, lymphocytes aligned in rows between those fibers, necrotic keratinocytes, often with preserved pyknotic nuclei, in all reaches of the epidermis, including the cornified layer, clustering of necrotic keratinocytes above elongated dermal papillae and vertical columns of parakeratosis with distinct dyskeratotic parakeratotic cells. CONCLUSION: In the absence of sclerosis, histopathologic diagnosis of LS depends on findings that are less distinctive. Nonetheless, a constellation of those findings allows a specific diagnosis to be made.

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.

Lichen Sclerosus of the Labial Mucosa: A Case Report and Literature Review.

Lichen sclerosus (LS) is an uncommon, chronic, inflammatory mucocutaneous disorder found predominantly in females with unknown etiology. It presents as a white sclerotic plaque commonly located on the anogenital area. Extragenital LS is less prevalent, and LS affecting the oral mucosa is extremely rare, with only 39 biopsy-confirmed cases reported in the literature. Due to its several mimicking conditions, histological examination is usually required for a definitive diagnosis, particularly in patients with oral LS. Current evidence-based treatment recommendations for oral LS are unavailable; however, most cases tend to improve after treatment with topical or intralesional corticosteroids. We report a case of a 58-year-old female referred from the otolaryngology department for evaluating an asymptomatic whitish sclerotic plaque on the lower lip mucosa that had existed for 1 year. Following a punch biopsy, the patient was diagnosed with LS of labial mucosa. The condition improved after 2 months of treatment with topical and intralesional corticosteroids. The present case report raises awareness in recognizing oral LS and contributes to knowledge of this rare disorder.

Giant cell lichenoid dermatitis within healed varicella zoster site.

There are dermatoses that arise within healed zosteriform sites, such as granulomas annulare, acneiform eruptions, psoriasis, lichen planus, and giant cell lichenoid dermatitis "GCLD." Nonetheless, graft-versus-host disease should be considered and ruled out, especially in patients post-bone marrow transplant. Herein, we report a case of GCLD manifesting within healed zosteriform sites.

Lichenoid dermatitis following PD-1 inhibitor-induced toxic epidermal necrolysis: a case report and literature review.

Immune checkpoint inhibitors such as anti-PD-1 receptor antibodies have been shown to be effective in patients with advanced gastric cancer. However, there is a growing concern about immune-related adverse events. A case of a patient with gastric adenocarcinoma who developed toxic epidermal necrolysis (TEN) induced by sintilimab and subsequently developed lichenoid dermatitis is reported. TEN was diagnosed according to a history of sintilimab use, clinical symptoms and physical examination. During hospitalization, the patient developed recurrent fever caused by bacteremia and recovered from TEN after anti-infection and anti-inflammatory treatments. However, when TEN was controlled, the patient developed the lesional manifestations of lichenoid dermatitis. To date, no cases of lichenoid dermatitis after TEN have been reported following the use of PD-1 inhibitors.

PD-1 inhibitors are drugs that help fight stomach cancer but can sometimes cause skin problems. Most skin problems are minor and do not have a serious impact on the patient's health. However, life-threatening skin problems such as toxic epidermal necrolysis (TEN) can sometimes happen. This case report describes a patient with stomach cancer who had lichenoid dermatitis (another skin problem) after TEN, following the treatment of his cancer with PD-1 inhibitors. To the best of our knowledge, it is very rare to experience both skin problems after treating cancer with PD-1 inhibitors. This rare phenomenon is reported to bring more attention to it. More research is needed to determine how to treat this problem better.

Occult squamous cell carcinoma within lichenoid dermatitis: three examples of cryptic cancer detection.

Lichenoid dermatitis can be a perplexing entity encompassing an array of cutaneous disorders. Two hundred forty-three (243) cases of otherwise unclassifiable lichenoid dermatitis were examined histologically employing a special cytokeratin stain. Occult squamous cell carcinoma was detected in three of the 243 cases, uncovered by special immunohistochemistry staining within histologic specimens of lichenoid dermatitis. We recommend staining for cutaneous cancer becoming a routine practice in evaluating cutaneous lichenoid dermatitis.