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American Family Physician Oct 2019Hand-foot-and-mouth disease is caused by human enteroviruses and coxsackieviruses. Outbreaks can occur in the spring to fall and are common in North America, and most... (Review)
Review
Hand-foot-and-mouth disease is caused by human enteroviruses and coxsackieviruses. Outbreaks can occur in the spring to fall and are common in North America, and most cases occur in patients younger than 10 years. Hand-foot-and-mouth disease is transmitted by fecal-oral, oral-oral, and respiratory droplet contact. Patients present with a low-grade fever, a maculopapular or papulovesicular rash on the hands and soles of the feet, and painful oral ulcerations. Lesions usually resolve in seven to 10 days; however, in rare cases, patients may have neurologic or cardiopulmonary complications. The differential diagnosis for childhood rashes and oral enanthems is broad and includes erythema multiforme, herpes, measles, and varicella. Treatment is supportive and directed toward hydration and pain relief as needed with acetaminophen or ibuprofen. Oral lidocaine is not recommended, and antiviral treatment is not available. The best methods to prevent the spread of hand-foot-and-mouth disease are handwashing and disinfecting potentially contaminated surfaces and fomites.
Topics: Animals; Child; Child, Preschool; Diagnosis, Differential; Exanthema; Female; Hand, Foot and Mouth Disease; Humans; Infant; Male
PubMed: 31573162
DOI: No ID Found -
Dermatologic Clinics Oct 2019Graft-versus-host disease (GVHD) is an adverse immunologic phenomenon following allogenic hematopoietic stem cell transplant. Cutaneous manifestations are the earliest... (Review)
Review
Graft-versus-host disease (GVHD) is an adverse immunologic phenomenon following allogenic hematopoietic stem cell transplant. Cutaneous manifestations are the earliest and most common presentation of the disease. This article describes the pathophysiology, clinical presentation, diagnosis, and treatment options available for acute and chronic GVHD. Acute and chronic GVHD result from an initial insult triggering an exaggerated inflammatory cascade. Clinical presentation for cutaneous acute GVHD is limited to maculopapular rash and oral mucosal lesions, whereas chronic GVHD can also include nail, scalp, and genitalia changes. Diagnosis is often made clinically and supported by biopsy, laboratory and radiology findings.
Topics: Acute Disease; Adrenal Cortex Hormones; Antibodies, Monoclonal; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunotherapy, Adoptive; Skin Diseases; T-Lymphocytes; Transplantation Conditioning; Transplantation, Homologous
PubMed: 31466596
DOI: 10.1016/j.det.2019.05.014 -
The Australasian Journal of Dermatology Feb 2021Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and... (Review)
Review
Mastocytosis is a rare disease characterised by expansion and collection of clonal mast cells in various organs including the skin, bone marrow, spleen, lymph nodes and gastrointestinal tract. The prevalence of mastocytosis has been estimated to be one in 10 000, while the estimated incidence is one per 100 000 people per year. Cutaneous mastocytosis is classified into (i) maculopapular cutaneous mastocytosis, also known as urticaria pigmentosa; (ii) diffuse cutaneous mastocytosis; and (iii) mastocytoma of the skin. In adults, cutaneous lesions are usually associated with indolent systemic mastocytosis and have a chronic evolution. Paediatric patients, on the contrary, have often cutaneous manifestations without systemic involvement and usually experience a spontaneous regression. Diagnosis of cutaneous mastocytosis may be challenging due to the rarity of the disease and the overlap of cutaneous manifestations. This short review describes pathogenesis and clinical aspects of cutaneous mastocytosis with a focus on diagnosis and currently available therapies.
Topics: Genetic Predisposition to Disease; Humans; Mastocytosis, Cutaneous; Phospholipases; Physician's Role; Prognosis; Skin; Tryptases; Urticaria Pigmentosa
PubMed: 33040350
DOI: 10.1111/ajd.13443 -
Journal of Cutaneous Medicine and... 2021Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell... (Review)
Review
Immune checkpoint inhibitors have proven to be efficacious for a broad spectrum of solid organ malignancies. These monoclonal antibodies lead to cytotoxic T-cell activation and subsequent elimination of cancer cells. However, they can also lead to immune intolerance and immune-related adverse event (irAEs) that are new and specific to these therapies. Cutaneous irAEs are the most common, arising in up to 34% of patients on PD-1 inhibitors and 43% to 45% on CTLA-4 inhibitors. The most common skin manifestations include maculopapular eruption, pruritus, and vitiligo-like lesions. A grading system has been proposed, which guides management of cutaneous manifestations based on the percent body surface area (BSA) involved. Cutaneous irAEs may prompt clinicians to reduce drug doses, add systemic steroids to the regiment, and/or discontinue lifesaving immunotherapy. Thus, the goal is for early identification and concurrent management to minimize treatment interruptions. We emphasize here that the severity of the reaction should not be graded based on BSA involvement alone, but rather on the nature of the primary cutaneous pathology. For instance, maculopapular eruptions rarely affect <30% BSA and can often be managed conservatively with skin-directed therapies, while Stevens-Johnson syndrome (SJS) affecting even 5% BSA should be managed aggressively and the immunotherapy should be discontinued at once. There is limited literature available on the management of the cutaneous irAEs and most studies present anecdotal evidence. We review the management strategies and provide recommendations for psoriatic, immunobullous, maculopapular, lichenoid, acantholytic eruptions, vitiligo, alopecias, vasculitides, SJS/toxic epidermal necrolysis, and other related skin toxicities.
Topics: Alopecia Areata; Body Surface Area; Drug Eruptions; Humans; Immune Checkpoint Inhibitors; Lichenoid Eruptions; Neoplasms; Pemphigoid, Bullous; Psoriasis; Severity of Illness Index; Stevens-Johnson Syndrome; Vasculitis; Vitiligo
PubMed: 32746624
DOI: 10.1177/1203475420943260 -
Cutaneous and Ocular Toxicology Mar 2022The therapeutic use of humanised monoclonal programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) and programmed cell death ligand-1 (PD-L1) (atezolizumab,... (Review)
Review
INTRODUCTION
The therapeutic use of humanised monoclonal programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) and programmed cell death ligand-1 (PD-L1) (atezolizumab, avelumab, durvalumab) immune checkpoint inhibitors (ICPi) as potent anticancer therapies is rapidly increasing. The mechanism of signalling of anti-PD-1/PD-L1 involves triggering cytotoxic CD4+/CD8 + T cell activation and subsequent abolition of cancer cells which induces specific immunologic adverse events that are specific to these therapies. These drugs can cause numerous cutaneous reactions and are characterized as the most frequent immune-related adverse events (irAEs). Majority of cutaneous irAEs range from non-specific eruptions to detectible skin manifestations, which may be self-limiting and present acceptable skin toxicity profiles, while some may produce life-threatening complications.
OBJECTIVE
This review aims to illuminate the associated cutaneous irAEs related to drugs used in oncology along with the relevant mechanism(s) and management.
AREAS COVERED
Literature was searched using various databases including Pub-Med, Google Scholar, and Medline. The search mainly involved research articles, retrospective studies, case reports, and clinicopathological findings. With this review article, an overview of the cutaneous irAEs with anti-PD-1/PD-L1 therapy, as well as suggestions, have been provided, so that their recognition at early stages could help in better management and would prevent treatment discontinuation.HIGHLIGHTSCutaneous adverse effects are the most prevalent immune-related adverse events induced by anti-PD-1/PD-L1 immune-checkpoint antibodies.Cutaneous toxicities mainly manifest in the form of maculopapular rash and pruritus.More specific cutaneous complications can also occur, including vitiligo, worsened psoriasis, lichenoid dermatitis, mucosal involvement (e.g. oral lichenoid reaction), dermatomyositis, lupus erythematosus.Cutaneous manifestations can be life-threatening including Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN).Dermatologic toxicities are usually mild, readily manageable, and rarely result in significant morbidity.Adequate management of the cutaneous adverse event and recognition in early stages could lead to the prevention of worsening of the lesions and limit treatment disruption.
Topics: B7-H1 Antigen; Humans; Immune Checkpoint Inhibitors; Neoplasms; Programmed Cell Death 1 Receptor; Retrospective Studies; Skin Diseases; Stevens-Johnson Syndrome
PubMed: 35107396
DOI: 10.1080/15569527.2022.2034842 -
American Journal of Clinical Dermatology Jun 2018The development of immune checkpoint inhibitors [monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1... (Review)
Review
The development of immune checkpoint inhibitors [monoclonal antibodies targeting cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) or programmed death ligand 1 (PD-L1)] represents a major breakthrough in cancer therapy. Although they present a favorable risk/benefit ratio, immune checkpoint blockade therapies have a very specific safety profile. Due to their unique mechanism of action, they entail a new spectrum of adverse events that are mostly immune related [immune-related adverse events (irAEs)], notably mediated by the triggering of cytotoxic CD4+/CD8+ T cell activation. Cutaneous toxicities appear to be one of the most prevalent irAEs, both with anti-PD-1 and anti-CTLA-4 agents or with the newly developed anti-PD-L1 agents, which corresponds to a class effect. They are observed in more than one-third of the treated patients, mainly in the form of a maculopapular rash (eczema-like spongiotic dermatitis) and pruritus. A wide range of other dermatologic manifestations can also occur, including lichenoid reactions, psoriasis, acneiform rashes, vitiligo-like lesions, autoimmune skin diseases (e.g., bullous pemphigoid, dermatomyositis, alopecia areata), sarcoidosis or nail and oral mucosal changes. In addition, the use of anti-CTLA-4 and anti-PD-1 therapies in combination is associated with the development of more frequent, more severe and earlier cutaneous irAEs compared to single agents. In most cases, these dysimmune dermatologic adverse events remain self-limiting and readily manageable. Early recognition and adequate management, however, are critical to prevent exacerbation of the lesions, to limit treatment interruption and to minimize quality of life impairment. This review describes the variable clinical and histopathologic aspects of dermatologic irAEs induced by immune checkpoint inhibitors. Appropriate treatment and counseling are also proposed, with a step-by-step approach for optimized management by both practicing oncologists and dermatologists.
Topics: Antineoplastic Agents, Immunological; Autoimmune Diseases; B7-H1 Antigen; CTLA-4 Antigen; Dermatologic Agents; Drug Eruptions; Humans; Immunotherapy; Incidence; Neoplasms; Phototherapy; Programmed Cell Death 1 Receptor; Quality of Life; Risk Factors; Severity of Illness Index; Skin; Treatment Outcome; Withholding Treatment
PubMed: 29256113
DOI: 10.1007/s40257-017-0336-3 -
American Journal of Clinical Dermatology Nov 2018Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in... (Review)
Review
Targeted therapies and immunotherapies are associated with a wide range of dermatologic adverse events (dAEs) resulting from common signaling pathways involved in malignant behavior and normal homeostatic functions of the epidermis and dermis. Dermatologic toxicities include damage to the skin, oral mucosa, hair, and nails. Acneiform rash is the most common dAE, observed in 25-85% of patients treated by epidermal growth factor receptor and mitogen-activated protein kinase kinase inhibitors. BRAF inhibitors mostly induce secondary skin tumors, squamous cell carcinoma and keratoacanthomas, changes in pre-existing pigmented lesions, as well as hand-foot skin reactions and maculopapular hypersensitivity-like rash. Immune checkpoint inhibitors (ICIs) most frequently induce nonspecific maculopapular rash, but also eczema-like or psoriatic lesions, lichenoid dermatitis, xerosis, and pruritus. Of the oral mucosal toxicities observed with targeted therapies, oral mucositis is the most frequent with mammalian target of rapamycin (mTOR) inhibitors, followed by stomatitis associated to multikinase angiogenesis and HER inhibitors, geographic tongue, oral hyperkeratotic lesions, lichenoid reactions, and hyperpigmentation. ICIs typically induce oral lichenoid reactions and xerostomia. Targeted therapies and endocrine therapy also commonly induce alopecia, although this is still underreported with the latter. Finally, targeted therapies may damage nail folds, with paronychia and periungual pyogenic granuloma distinct from chemotherapy-induced lesions. Mild onycholysis, brittle nails, and a slower nail growth rate may also be observed. Targeted therapies and immunotherapies often profoundly diminish patients' quality of life, which impacts treatment outcomes. Close collaboration between dermatologists and oncologists is therefore essential.
Topics: Antineoplastic Agents; Dermatology; Drug Eruptions; Hair; Humans; Immunotherapy; Interdisciplinary Communication; Medical Oncology; Molecular Targeted Therapy; Mouth Mucosa; Nails; Neoplasms; Quality of Life; Skin; Treatment Outcome
PubMed: 30374901
DOI: 10.1007/s40257-018-0384-3 -
British Journal of Clinical Pharmacology Aug 2022Drug-induced skin disease or cutaneous adverse drug reactions (CADRs) are terms that encompass the clinical manifestations of the skin, mucosae and adnexa induced by a... (Review)
Review
Drug-induced skin disease or cutaneous adverse drug reactions (CADRs) are terms that encompass the clinical manifestations of the skin, mucosae and adnexa induced by a drug or its metabolites. The skin is the organ most frequently affected by drug reactions, which may affect up to 10% of hospitalized patients and occur in 1-3% of multimedicated patients. Most CADRs are mild or self-resolving conditions; however, 2-6.7% of could develop into potentially life-threatening conditions. CADRs represent a heterogeneous field and can be diagnostically challenging as they may potentially mimic any dermatosis. Currently, there are between 29-35 different cutaneous drug-reaction patterns reported ranging from mild dermatitis to an extensively burnt patient. The most frequently reported are maculopapular rash, urticaria/angioedema, fixed drug eruption and erythema multiforme. Less common but more severe patterns include erythroderma, drug reaction with eosinophilia and systemic symptoms, and Stevens-Johnson syndrome/toxic epidermal necrolysis spectrum. Almost any drug can induce a CADR, but antibiotics, nonsteroidal anti-inflammatory drugs and antiepileptics are the most frequently involved. Different mechanisms are involved in the pathogenesis of CADRs, although in some cases, these remain still unknown. CADRs could be classified in different ways: (i) type A (augmented) or type B (bizarre); (ii) immediate or delayed; (iii) immune-mediated or nonimmune-mediated; (iv) nonsevere or life-threatening; and (v) by their phenotype, including exanthematous, urticarial, pustular and blistering morphology. Recognizing a specific CADR will mostly depend on the ability of the physician to perform a detailed clinical examination, the proper description of the morphology of the skin lesions and supporting laboratory and/or skin biopsy findings.
PubMed: 35974692
DOI: 10.1111/bcp.15490 -
Cureus Oct 2020Dyshidrotic eczema (DE) or acute palmoplantar eczema is a common cause of hand and foot dermatitis in adults. It is a recurrent vesicular eruption affecting the soles,...
Dyshidrotic eczema (DE) or acute palmoplantar eczema is a common cause of hand and foot dermatitis in adults. It is a recurrent vesicular eruption affecting the soles, palms, or both. It is very pruriginous and generally appears suddenly. It creates vesicles that, on physical examination, can look similar to "tapioca pudding", which is the characteristic clinical feature of this disorder. It is more common in young adults and affects men and women equally. In this report, we present the case of a 56-year-old man with no relevant past medical history who presented to the hospital with vesicular lesions in his hands and maculopapular lesions in his arms and legs. The patient had characteristic lesions in his right hand consistent with DE and negative workup for bullous pemphigoid, scabies, and bacterial, fungal, and viral infections.
PubMed: 33173645
DOI: 10.7759/cureus.10839