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Mucositis

 

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Mucositis



 
 
Mucositis is the painful inflammation
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
 and ulceration
Peptic ulcer

A peptic ulcer, also known as ulcus pepticum, PUD or peptic ulcer disease, is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful....
 of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy
Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
 and radiotherapy treatment for cancer.

Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy.






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Mucositis is the painful inflammation
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
 and ulceration
Peptic ulcer

A peptic ulcer, also known as ulcus pepticum, PUD or peptic ulcer disease, is an ulcer of an area of the gastrointestinal tract that is usually acidic and thus extremely painful....
 of the mucous membranes lining the digestive tract, usually as an adverse effect of chemotherapy
Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
 and radiotherapy treatment for cancer.

Oral and gastrointestinal (GI) mucositis can affect up to 100% of patients undergoing high-dose chemotherapy and hematopoietic stem cell transplantation, 80% of patients with malignancies of the head and neck receiving radiotherapy, and a wide range of patients receiving chemotherapy. Alimentary track mucositis increases mortality and morbidity and contributes to rising health care costs.Cancer. 2004 May 1;100(9 Suppl):2026-46. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Rubenstein EB, et al. [PMID15108223] Expert panel reviewed literature published January 1966 to May 2002, to create evidence-based guidelines for the Multinational Association of Supportive Care in Cancer and the International Society for Oral Oncology.

For most cancer treatment, about 5-15% of patients get mucositis. However, with 5-fluorouracil
Fluorouracil

Fluorouracil is a pyrimidine analog, which is used as a medication in the treatment of cancer. It belongs to the family of drugs called antimetabolites....
 (5-FU), up to 40% get mucositis, and 10-15% get grade 3-4 oral mucositis. Irinotecan
Irinotecan

Irinotecan is a chemotherapy agent that is a Type I topoisomerase Enzyme inhibitor. Chemically, it is a semisynthetic analogue of the natural alkaloid camptothecin....
 is associated with severe GI mucositis in over 20% of patients. 75-85% of bone marrow transplantation recipients experience mucositis, of which oral mucositis is the most common and most debilitating, especially when melphalan is used. In grade 3 oral mucositis, the patient is unable to eat solid food, and in grade 4, the patient is unable to consume liquids as well.

Radiotherapy to the head and neck or to the pelvis or abdomen is associated with Grade 3 and Grade 4 oral or GI mucositis, respectively, often exceeding 50% of patients. Among patients undergoing head and neck radiotherapy, pain and decreased oral function may persist long after the conclusion of therapy. Fractionated radiation dosage increases the risk of mucositis to > 70% of patients in most trials. Oral mucositis is particularly profound and prolonged among HSCT recipients who receive total-body irradiation.

Pathophysiology

The pathophysiology
Pathophysiology

Pathophysiology is the study of the disturbance of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from a disease or abnormal syndrome, or condition that may not qualify to be called a disease....
 of mucositis can be divided into its 5 stages; including an initiation phase, a message generation phase, a signaling and amplification phase, an ulceration phase, and a healing phase. Different cytokine
Cytokine

Cytokines are a category of signaling molecules that, like hormones and neurotransmitters, are used extensively in cell communication. They are proteins, peptides or glycoproteins....
s are responsible for the various stages. The initiation phase is caused by the production of free radicals caused by the chemo- or radio- therapy, which damages cell DNA
DNA

Deoxyribonucleic acid is a nucleic acid that contains the genetics instructions used in the development and functioning of all known living organisms and some viruses....
. This causes the production of cell transcription factors such as NFkB, which upregulates inflammatory cytokines, marking the beginning of the ulceration phase. Main inflammatory cytokines involved are IL-1 and TNF-alpha. During the healing phase, epithelial cells are attracted to the site of the ulcer and begin the re-epithelialization of the ulcers.

Clinical manifestations

Cancer
Cancer

Cancer is a class of diseases in which a group of cell display uncontrolled growth , invasion , and sometimes metastasis . These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize....
 patients undergoing chemotherapy usually become symptomatic four to five days after beginning treatment, reaching a peak at around day 10, and then slowly improving over the course of a few weeks. Mucositis associated with radiotherapy usually appears at the end of the second week of treatment and may last for six to eight weeks.

As a result of cell death in reaction to chemo- or radio-therapy, the mucosal lining of the mouth becomes thin, may slough off and then become red, inflamed and ulcerated. The ulcers may become covered by a yellowish white fibrin clot called a pseudomembrane. Peripheral erythema
Erythema

Erythema is redness of the skin caused by capillary congestion....
 is usually present. Ulcers may range from 0.5 cm to greater than 4 cm. Oral mucositis can be severely painful. The degree of pain is usually related to the extent of the tissue damage. Pain is often described as a burning sensation accompanied by reddening. Due to pain, the patient may experience trouble speaking, eating, or even opening the mouth.

Dysgeusia
Dysgeusia

Dysgeusia is the distortion or decrease of the sense of taste. Dysgeusia is associated with zinc deficiency and some drugs designed to treat hypertension and anxiety, including lithium....
, or an alteration in taste perception, is common, especially for those who are receiving concomitant radiation therapy to the neck and mouth area. "Taste blindness," or an altered sense of taste, is a temporary condition that occurs because of effects on taste buds that are mostly located in the tongue. Sometimes, only partial recovery of taste occurs. Common complaints are of food tasting too sweet or too bitter or of a continuous metallic taste.

Diagnosis

Diagnosis is based on the symptoms the patient is experiencing and the appearance of the tissues of the mouth following chemotherapy
Chemotherapy

Chemotherapy, in its most general sense, refers to treatment of disease by chemicals that kill cells, specifically those of micro-organisms or cancer....
, bone marrow
Bone marrow

Bone marrow is the flexible biological tissue found in the hollow interior of bones. In adults, marrow in large bones produces new blood cells....
 transplants or radiotherapy. Red burn-like sores or ulcers throughout the mouth is enough to diagnose mucositis.

Treatment

Treatment of mucositis is mainly supportive. Oral hygiene
Oral hygiene

Teeth cleaning is the removal of dental plaque from teeth, in order to prevent Dental caries , gingivitis, and Periodontal disease. It is part of a complete program of oral hygiene....
 is the mainstay of treatment; patients are encouraged to clean their mouth every four hours and at bedtime, more often if the mucositis becomes worse. Water-soluble jellies can be used to lubricate the mouth. Salt mouthwash can soothe the pain and keep food particles clear so as to avoid infection. Patients are also encouraged to drink plenty of liquids, at least three liters a day, and avoid alcohol. Citrus fruits, alcohol, and foods that are hot are all known to aggravate mucositis lesions. Medicinal mouthwashes may be used such as Chlorhexidine gluconate and viscous Lidocain for relief of pain. Palifermin
Palifermin

Palifermin is a human recombinant DNA keratinocyte growth factor produced in Escherichia coli.Palifermin costs 5,000 Euros per treatment for a 70 kg patient ...
 is a human KGF (keratinocyte growth factor) that has shown to enhance epithelial cell proliferation, differentiation, and migration. Experimental therapies have been reported, including the use of cytokines and other modifiers of inflammation
Inflammation

Inflammation is the complex biological response of Blood vessel tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurious stimuli as well as initiate the healing process for the tissue....
 (eg, IL-1, IL-11, TGF-beta3), amino acid
Amino acid

In chemistry, an amino acid is a molecule containing both amine and carboxyl functional groups. These molecules are particularly important in biochemistry, where this term refers to alpha-amino acids with the general formula H2NCHRCOOH, where R is an organic substituent....
 supplementation (eg, glutamine), vitamins, colony-stimulating factors, cryotherapy
Cryotherapy

Cryotherapy is the local or general use of low temperatures in medical therapy or the removal of heat from a body part. Its goal is to decrease cellular metabolism, increase cellular survival, decrease inflammation, decrease pain and spasm, promote vasoconstriction, and when using extreme temperatures, to destroy cells by crystalizing the cy...
, and laser therapy. Symptomatic relief of the pain of oral mucositis may be provided by barrier protection agents such as concentrated oral gel products such as Gelclair.

Complications

Sores or ulcerations can become infected by virus
Virus

A virus is a Optical microscope#Limitations of light microscopes infectious agent that is unable to grow or reproduce outside a host cell . Viruses infect all cellular life....
, bacteria
Bacteria

The Bacteria are a large group of unicellular microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals....
 or fungus
Fungus

A fungus is a Eukaryote organism that is a member of the Kingdom Fungi . The fungi are a monophyletic group, also called the Eumycota , that is phylogeny distinct from the morphologically similar slime molds and water molds ....
. Pain and loss of taste perception makes it more difficult to eat, which leads to weight loss. Ulcers may act as a site for local infection and a portal of entry for oral flora that, in some instances, may cause septicemia (especially in immunosuppressed patients). Approximately half of all patients who receive chemotherapy develop such severe OM that it becomes dose-limiting such that the patient's cancer treatment must be modified, compromising the prognosis.

General sources

Medical journal articles, guidelines, recommendations, and slides and videos from conference presentations.