Side-effects include suppression of myelocytes in bone marrow, in?ammation of mucous membranes, and, rarely, PNEUMONITIS. It should be avoided whenever signi?cant renal impairment is present, while signi?cant pleural e?usion or ascites is also a contraindication. Blood counts should be carefully monitored whenever intrathecal methotrexate is given. Oral or parenteral folinic acid helps to prevent, or to speed recovery from, myelosuppression or mucositis.
Methotrexate is used in dermatology, where it may be indicated for cases of severe uncontrolled PSORIASIS unresponsive to conventional therapy; it may also be indicated for severe active RHEUMATOID ARTHRITIS. Because of its potentially severe haematological, pulmonary, gastrointestinal, and other toxicities it should be used only by specialists and appropriate renal and liver function tests carried out before and during treatment. It should be avoided in pregnancy, and conception should be avoided for at least six months after stopping, as should breast feeding. Concurrent administration of aspirin or other NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) reduces methotrexate excretion, increasing its toxicity, and should therefore be avoided whenever possible.
The predisposition to psoriasis is genetic, multiple genes being involved, but postnatal factors such as acute infection, hormonal disturbance, pregnancy and drugs can in?uence or provoke it. The sexes are equally affected and onset is most common in the second or third decade of life.
The psoriatic lesion is dull red, scaly and well de?ned. Scale is shed constantly, either in tiny pieces or as large plaques. The scalp is usually affected but the disease does not cause signi?cant hair loss. The ?ngernails may be pitted or ridged and the toenails grossly thickened. Several clinical patterns occur: in guttate psoriasis, a sudden explosion of multiple tiny lesions may follow a streptococcal throat infection, especially in children. Larger lesions are characteristic of discoid (plaque) psoriasis, the usual adult form. In the elderly the plaques may be mainly in the large body folds – ?exural psoriasis. Rarely, psoriasis may be universal (psoriatic erythroderma), or a sterile pustular eruption may supervene (pustular psoriasis).
Mucous membranes in the mouth and elsewhere are not affected. Psoriasis does not affect internal organs, but in about 1 per cent of subjects an in?ammatory joint disease (psoriatic arthritis) may be associated with the condition.
Treatment There is no absolute cure, but several agents used topically are of value including coal-tar extracts, DITHRANOL, CORTICOSTEROIDS and synthetic derivatives of vitamins A and D. Ultraviolet B phototherapy (and natural sunlight) bene?ts most but not all psoriatics. Systemic therapy, including PHOTOCHEMOTHERAPY, is reserved for severe forms of psoriasis. METHOTREXATE, CICLOSPORIN A and oral RETINOIDS are the most e?ective drugs, but they are potentially dangerous and require expert monitoring.
Patient information may be obtained through the Psoriasis Association.... psoriasis
Ectopic pregnancy is more common in women who have had previous pelvic infections (see pelvic inflammatory disease) and with some types of IUD and progestogen-only oral contraceptives.
Most ectopic pregnancies are discovered in the first 2 months, often before the woman realizes she is pregnant. Symptoms usually include severe painin the lower abdomen and vaginal bleeding. Internal bleeding may cause symptoms of shock, such as pallor, sweating, and faintness.
Diagnosis is made by a transvaginal ultrasound examination and can be confirmed by ectopic laparoscopy. If the diagnosis is made early, medical treatment using the drug methotrexate may be considered. In most cases, surgery, usually minimally invasive surgery, to remove the pregnancy is carried out. If blood loss is severe, blood transfusions are needed. An affected fallopian tube is removed if it cannot be repaired.... ectopic pregnancy
Treatment Any major de?ciencies, such as thyroxin or insulin lack, should be corrected. The activity of the immune system should then be reduced. CORTICOSTEROIDS and, in more severe cases, strong immunosuppressant drugs – AZATHIOPRINE, CYCLOPHOSPHAMIDE or METHOTREXATE – should be administered. Treatment is di?cult because of the need to control the autoimmune condition without damaging the body’s ability to combat other diseases.... autoimmune disorders
Cytotoxic drugs are used either singly or in combination, when an enhanced response is the aim. Chemotherapy of cancer is a complex process and should be supervised by an oncologist in co-operation with physicians, surgeons, radiotherapists and radiologists as appropriate.
The cytotoxic drugs include:
(1) The alkylating agents which act by damaging DNA, thus interfering with cell reproduction. Cyclophosphamide, ifosfamide, chlorambucil, kelphalan, busulphan, thiotepa and mustine are examples of alkylating agents.
(2) There are a number of cytotoxic antibiotics used in the treatment of cancer – doxorubicin, bleomycin, dactinomycin, mithramycin and amsacrine are examples. They are used primarily in the treatment of acute leukaemia and lymphomas.
(3) Antimetabolites – these drugs combine irreversibly with vital enzyme systems of the cell and hence prevent normal cell division. Methotrexate, cytarabine, ?uorouracil, mercaptopurine and azathioprine are examples.
(4) Another group of cytotoxic drugs are the vinca alkaloids such as vincristine, vinblastine and vindesima.
(5) Platinum compounds such as carboplatin, cisplatin and oxaliplatin are e?ective. All of them are given intravenously, but the latter two tend to have more unpleasant side-effects. Carboplatin and cisplatin are useful in the treatment of solid tumours. Carboplatin, a derivative of cisplatin, is given intravenously in ovarian cancer and in small-cell lung cancer. Better tolerated than cisplatin, the drug causes less nausea and vomiting, nephrotoxicity, neurotoxicity and ototoxicity. Where platinum-containing therapy has failed, intravenous treatment with paclitaxel may be tried. With only a limited success rate, it is relatively toxic and should be carefully supervised; responses, however, are sometimes prolonged.
Also of increasing importance in treating cancer are interferons. These are naturally occurring proteins with complex effects on immunity and cell function. Although toxic, with numerous adverse effects, they have shown some anti-tumour e?ect against certain lymphomas and solid tumours.... cytotoxic
The drugs work by suppressing the production and activity of white blood cells called lymphocytes. Side effects vary, but all the drugs increase the risk of infection and of the development of certain cancers.... immunosuppressant drugs
There has been a rapid introduction in recent years of monoclonal antibodies which prevent T-cells from proliferating. They can be recognised by the su?x ‘mab’ (standing for monoclonal antibody) and include rituximab and alemtuzumab. In?iximab, used in CROHN’S DISEASE and RHEUMATOID ARTHRITIS, inhibits tumour necrosis factor alpha.... immunosuppression
According to the type of cells that predominate, leukaemia may be classi?ed as acute or chronic lymphoblastic leukaemia or myeloid leukaemia. Acute lymphoblastic leukaemia (ALL) is mostly a disease of childhood and is rare after the age of 25. Acute myeloid leukaemia is most common in children and young adults, but may occur at any age. Chronic lymphatic leukaemia occurs at any age between 35 and 80, most commonly in the 60s, and is twice as common in men as in women. Chronic myeloid leukaemia is rare before the age of 25, and most common between the ages of 30 and 65; men and women are equally affected. Around 2,500 patients with acute leukaemia are diagnosed in the United Kingdom, with a similar number annually diagnosed with chronic leukaemia.
Cause Both types of acute leukaemia seem to arise from a MUTATION in a single white cell. The genetically changed cell then goes through an uncontrolled succession of divisions resulting in many millions of abnormal white cells in the blood, bone marrow and other tissues. Possible causes are virus infection, chemical exposure, radiation and genetic background. The cause of chronic lymphocytic leukaemia is not known; the chronic myeloid version may have a genetic background.
Symptoms In acute cases the patient is pale due to anaemia, may have a purpuric rash due to lack of platelets, and may have enlarged lymphatic glands and spleen. The temperature is raised, and the condition may be mistaken for an acute infection (or may ?rst become apparent because the patient develops a severe infection due to a lack of normal white blood cells).
In the chronic type of the disease the onset is gradual, and the ?rst symptoms which occasion discomfort are either swelling of the abdomen and shortness of breath, due to painless enlargement of the spleen; or the enlargement of glands in the neck, armpits and elsewhere; or the pallor, palpitation, and other symptoms of anaemia which often accompany leukaemia. Occasional bleeding from the nose, stomach, gums or bowels may occur, and may be severe. Generally, there is a slight fever.
When the blood is examined microscopically, not only is there an enormous increase in the number of white cells, which may be multiplied 30- or 60-fold, but various immature forms are also found. In the lymphatic form of the disease, most white cells resemble lymphocytes, which, in healthy blood, are present only in small numbers. In the myeloid form, myelocytes, or large immature cells from the bone marrow, which are never present in healthy blood, appear in large numbers, and there may also be large numbers of immature, nucleated erythrocytes.
Treatment This varies according to the type of leukaemia and to the particular condition of the patient. Excellent results are being obtained in the control of ALL using blood transfusions, CHEMOTHERAPY, RADIOTHERAPY and bone-marrow TRANSPLANTATION. In the case of acute leukaemia, the drugs now being used include MERCAPTOPURINE, METHOTREXATE and CYCLOPHOSPHAMIDE. Blood transfusion and CORTICOSTEROIDS play an important part in controlling the condition during the period before a response to chemotherapy can be expected. Chemotherapy has almost completely replaced radiotherapy in the treatment of chronic leukaemia. For the myeloid form, BUSULFAN is the most widely used drug, replaced by hydroxyurea, mercaptopurine, or one of the nitrogen mustard (see NITROGEN MUSTARDS) derivatives in the later stages of the disease. For the lymphatic form, the drugs used are CHLORAMBUCIL, CYCLOPHOSPHAMIDE, and the nitrogen mustard derivatives.
Prognosis Although there is still no guaranteed cure, the outlook in both acute and chronic leukaemia has greatly improved – particularly for the acute form of the disease. Between 70 and 80 per cent of children with acute lymphoblastic leukaemia may be cured; between 20 and 50 per cent of those with acute myeloid leukaemia now have much-improved survival rates. Prognosis of patients with chronic lymphocytic leukaemia is often good, depending on early diagnosis.... leukaemia
Surgery may be most common, and is often the only treatment, for some gastrointestinal tumours, soft-tissue tumours, gynaecological tumours and advanced cancers of the head and neck.
Radiotherapy uses ionising radiation to kill tumour cells. Radiation is by naturally occurring isotopes (see ISOTOPE) or arti?cially produced X-RAYS. Germ-cell tumours (see SEMINOMA; TERATOMA) and malignant lymphomas (see LYMPHOMA) appear to be particularly sensitive to irradiation, and many head and neck tumours, gynaecological cancers, and localised cancers of the PROSTATE GLAND and URINARY BLADDER are curable with radiotherapy. It is also a valuable means of reducing pain from bone metastases (see METASTASIS). Unpleasant side-effects are common: chie?y lethargy, loss of appetite and dry, itchy skin symptoms.
Chemotherapy is also an important treatment in germ-cell tumours (see above); in some forms of LEUKAEMIA and lymphoma; in ovarian cancer (following surgery – see OVARIES, DISEASES OF); and in small-cell lung cancer (although most patients die within 18 months – see LUNGS, DISEASES OF). It is also used in some breast cancers (see BREASTS, DISEASES OF); advanced myeloma (see MYELOMATOSIS); sarcomas (see under CANCER); and some childhood cancers (such as WILMS’ TUMOUR).
More than 20 substances are in common use, the major classes being ALKYLATING AGENTS (e.g. cyclophosphamide, chlorambucil, busul fan); ANTIMETABOLITES (e.g. methotrexate); VINCA ALKALOIDS (e.g. vincristine, vinblastine); and antitumour ANTIBIOTICS (e.g. actinomycin D). Choice of agent and the appropriate regimen requires expert guidance. Common side-effects include nausea and vomiting, bone-marrow suppression and ALOPECIA, with each substance having its own spectrum of unwanted effects.
Good doctor-patient communication, with the sharing of information and bringing the patient into the decision-making process, is vital even if time-consuming and exhausting.
Equally imortant treatment is PALLIATIVE, for example to ensure e?ective pain or nausea control. Common sources of pain in cancer may involve bone, nerve compression, soft tissue, visceral, myofascial, constipation, muscle spasm, low-back pain, joint pain (e.g. capsulitis) and chronic post-operative pain. Patients may be suffering from more than one pain, all of which should be identi?ed. The aim should be to eliminate pain.
There are three rungs of the analgesic ladder; if one rung fails, the next one should be tried:
(1) non-opioid drugs – for example, aspirin, PARACETAMOL, NON-STEROIDAL ANTIINFLAMMATORY DRUGS (NSAIDS); (2) weak opioids – for example, CODEINE, DIHYDROCODEINE, dextropropoxyphene; (3) strong opioids
– for example, MORPHINE, DIAMORPHINE, buprenorphine. Oral treatment is always preferable, unless prevented by severe vomiting. (See also CANCER; ONCOLOGIST; PAIN; PALLIATIVE CARE.)... oncology
Causes There is a major immunogenetic predisposition to rheumatoid arthritis in people carrying the HLA-DR4 antigen (see HLA SYSTEM). Other minor immunogenetic factors have also been implicated. In addition, there is a degree of familial clustering which suggests other unidenti?ed genetic factors. Genetic factors cannot alone explain aetiology, and environmental and chance factors must be important, but these have yet to be identi?ed.
Epidemiology Rheumatoid arthritis more commonly occurs in women from the age of 30 onwards, the sex ratio being approximately 4:1. Typical rheumatoid arthritis may occur in adolescence, but in childhood chronic SYNOVITIS usually takes one of a number of di?erent patterns, classi?ed under juvenile chronic arthritis.
Pathology The primary lesion is an in?ammation of the synovial membrane of joints. The synovial ?uid becomes diluted with in?ammatory exudate: if this persists for months it leads to progressive destruction of articular CARTILAGE and BONE. Cartilage is replaced by in?ammatory tissue known as pannus; a similar tissue invades bone to form erosions. Synovitis also affects tendon sheaths, and may lead to adhesion ?brosis or attrition and rupture of tendons. Subcutaneous and other bursae may be involved. Necrobiotic nodules also occur at sites outside synovium, including the subcutaneous tissues, the lungs, the pericardium and the pleura.
Clinical features Rheumatoid arthritis varies from the very mild to the severely disabling. Many mild cases probably go undiagnosed. At least 50 per cent of patients continue to lead a reasonably normal life; around 25 per cent are signi?cantly disabled in terms of work and leisure activities; and a minority become markedly disabled and are limited in their independence. There is often an early acute phase, followed by substantial remission, but in other patients gradual step-wise deterioration may occur, with progressive involvement of an increasing number of joints.
The diagnosis of rheumatoid arthritis is largely based on clinical symptoms and signs. Approximately 70 per cent of patients have rheumatoid factor ANTIBODIES in the SERUM but, because of the large number of false positives and false negatives, this test has very little value in clinical practice. It may be a useful pointer to a worse prognosis in early cases if the level is high. X-RAYS may help in diagnosing early cases and are particularly helpful when considering surgery or possible complications such as pathological fracture. Patients commonly develop ANAEMIA, which may be partly due to gastrointestinal blood loss from antiin?ammatory drug treatment (see below).
Treatment involves physical, pharmacological, and surgical measures, together with psychological and social support tailored to the individual patient’s needs. Regular activity should be maintained. Resting of certain joints such as the wrist with splints may be helpful at night or to assist prolonged manual activities. Sound footwear is important. Early use of antirheumatic drugs reduces long-term disability. Drug treatment includes simple ANALGESICS, NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS), and slow-acting drugs including GOLD SALTS (in the form of SODIUM AUROTHIOMALATE), PENICILLAMINE, SULFASALAZINE, METHOTREXATE and AZATHIOPRINE.
The non-steroidal agents are largely e?ective in reducing pain and early-morning sti?ness, and have no e?ect on the chronic in?ammatory process. It is important, especially in the elderly, to explain to patients the adverse effects of NSAIDs, the dosage of which can be cut by prescribing paracetamol at the same time. Combinations of anti-rheumatic drugs seem better than single agents. The slow-acting drugs take approximately three months to act but have a more global e?ect on chronic in?ammation, with a greater reduction in swelling and an associated fall in erythrocyte sedimentation rate (ESR) and rise in the level of HAEMOGLOBIN. Local CORTICOSTEROIDS are useful, given into individual joints. Systemic corticosteroids carry serious problems if continued long term, but may be useful under special circumstances. Much research is currently going on into the use of tumour necrosis factor antagonists such as INFLIXIMAB and etanercept, but their precise role remains uncertain.... rheumatoid arthritis
Health Encyclopedia