Anemia is a disorder of the blood. When the red blood cells change in number or in shape, the rest of the body, including the heart and lungs, suffers. The hemoglobin in the blood, the iron-containing oxygen-transport protein, cannot carry enough oxygen to the rest of the body. All cells, tissues and organs need oxygen to carry out their functions and produce energy. Without oxygen delivery, a person exhausts easily.
The body responds to anemia and low oxygen delivery with neuronal nitric oxide synthase (nNOS), an enzyme which helps the body adapt and use oxygen more efficiently. Long-term however, anemia can cause damage, especially neurocognitively. There are two major types of anemia, ACD and IDA. The rare anemia disorders can be very complicated and require a hematologist’s expert opinion to diagnose.
Types of Anemia
Anemia of Chronic Disease (ACD)
An underlying disorder or condition causes immune system activation and anemia. Inflammation mediates and decreases red blood cell count (RBC) production, and sometimes, existing RBCs may have a shortened life span. The term ACD is common but sometimes misleading, as the generic term is sometimes applied to anemic syndromes caused by drugs given for a condition. The usual definition encompasses:
- after major trauma and surgery
- acute and chronic infections
- autoimmune disorders
- other severe illnesses
New research suggests that anemia is an adaptive physiologic response to disease and patients may fare better if the anemia is NOT aggressively treated. Some scientists now believe that anemia treatment to raise hemoglobin levels may lead to earlier death and that physicians should do a better job in finding the exact cause of the anemia.
Iron-Deficient Anemia (IDA)
Diagnosis of IDA prompts an investigation into the cause. Iron deficiency results from excessive iron requirements (ex. athletes and pregnant women), inadequate iron intake (ex. low economic status), or increased iron loss (ex. menstruating women). Lack of iron in the body causes shortness of breath (dyspnea), pale skin color (pallor), fatigue, and appetite for non-food items. A clinical examination and a history interview attempts to find the underlying cause. About 25 percent of the population, mostly women and children, have iron deficiency without rising to the level of diagnosed IDA. Official classification of IDA includes low serum iron and other biomarkers including:
- Microcytic – abnormally small red blood cells.
- Hypochromic – decrease in the concentration of corpuscular hemoglobin.
- Low reticulocyte count – the body’s production of immature red blood cells.
- Increased total iron-binding capacity (TIBC) – transferrin’s ability to transport iron.
- Less than 16% transferrin saturation – the ratio of serum iron and total iron-binding capacity, multiplied by 100.
- Low serum ferritin – ferritin stores iron, and releases it in a controlled manner.
Sickle Cell Anemia– a hereditary disease which causes blood cells to form a crescent or sickle shape. These fragile cells cannot deliver enough oxygen to the tissues and often get stuck in the blood flow. This is a very severe and painful disease, often requiring hospitalization. Patients experience agonizing pain in the skeleton, chest, and/or abdomen. Patients may also have a high temperature, infection, pneumonia-like symptoms and heart problems. Sickle cell is handed down from parents to children. If one parent has the sickle cell gene, the child will be a carrier. If both parents have the sickle cell gene, the child will have sickle cell disease. Currently, scientists believe that the gene mutated many years ago in order to mount a defense against Malaria.
Aplastic Anemia – the bone marrow does not produce enough platelets, red blood cells and white blood cells. Often, no cause is identified, or the cause is an attack on the bone marrow by the white blood cells. In other cases, drugs or toxins can reduce the bone marrow’s ability to produce sufficient new cells.
Sideroplastic Anemia – may be a hereditary disease which is characterized by inefficient hemoglobin biosynthesis in the bone marrow. The hemoglobin fails to incorporate iron, or fails to sense iron and oxygen, resulting in deficits of normal levels of iron in cellular compartments.
Toxins or Mineral deficiencies – anemia symptoms can occur due to a copper deficiency, and lead or aluminum intoxication due to exposure to lead paint and other hazards. Some cases may be hereditary.
Iron Refractory Anemia – the gene TMPRSS6 is mutated and causes inhibition of iron absorption and iron release mechanisms.
Fanconi Anemia – a defect in the genes causes deficits in oxygen delivery, fighting infection and forming blood clots. The DNA is unable to repair itself because the FANCA protein cannot reach the cell nucleus. Patients often develop cancer and die by the age of thirty.
Congenital Dyserythropoietic Anemia – ineffective erythropoiesis (low concentration of hemoglobin and reduced amounts of reticulocytes) caused by a mutation in the SEC23B gene. Researchers believe that the mutation began around the time of the Roman empire in Italy.
Autoimmune Hemolytic Anemia – may begin very quickly and be very serious as the immune system attacks itself. Half of all cases have an unknown cause and the other half are caused by medications or another disease.
Diamond-Blackfan Anemia – mutations in the RPS19 gene are thought to cause some cases. Patients often have deformities and heart defects and are diagnosed within two years of birth. Patients live an average of 40 years.
Postpartum Anemia – about half of all women, as high as 80% of women in some countries, develop anemia after giving birth to a child. Women who were anemic before giving birth and women who suffer extreme blood loss during birth have the highest risk. Postpartum anemia is a major health problem for new mothers and may be partially responsible for postpartum depression and emotional instability.
The true number of chronic anemia cases may not be known, as many conditions and diseases cause immune system activation. About eighty percent of people who require hospitalization for serious conditions will develop anemia. Many chronic renal failure patients and rheumatoid arthritis patients have chronic anemia. About 10 percent of older people, who often have more diseases and poor diet, have chronic anemia.
Iron deficiency anemia incidence varies greatly by country. Developed countries may have between 3 to 8 percent incidence in the population. Developing countries with lower economic status and nutritional deficiencies, may have as high as 80 percent incidence in the population. However, these rates are declining as governments are moving to fortify food products with iron. Blood loss is the most common precipitating event but other causes of IDA include:
- Inadequate diet
- Impaired absorption
- Heavy menstruation
- Athletic pursuits
- Blood donation
- Gastric surgery
- Celiac disease
- Gastrointestinal disorder
- Hiatal hernia
- H. pylori infection
- Unknown causes
Chronic Anemia results in serious complications including:
- Cardiac failure
- Acute renal failure
- Lung injury
- Tumor and Cancer
- Gastric Bypass Surgery
- Respiratory Disease
Iron-Deficient Anemia in pregnant women and children impairs the developing child and cannot always be repaired. Even mild anemia can have long-lasting effects on the brain and the body. Other complications for people of all ages, races and gender of include:
- Performance – athletes with iron deficiencies do not perform as well.
- Growth delays in infants and children.
- Developmental delay
- Cognitive impairment
- Mood disorders
- Learning problems and attention deficits
- Preterm births
- Heart failure
Symptoms of mild, moderate or severe anemia of any cause:
- Pallor – looking pale or yellow color or looking different than normal.
- Fatigue – tiring easily or a rapid loss of energy.
- Weakness – not having enough energy or strength.
- Decreased exercise tolerance – feeling short of breath when attempting to exercise.
- Feeling dizzy or lightheaded.
- Passing out or fainting.
- Irregular heart beating.
- Having symptoms of an underlying disorder like fever, weight loss, night sweats, stiff joints, rash or hives.
- Being an intensive care patient in the hospital.
- Having an autoimmune disorder like rheumatoid arthritis and inflammatory bowel disease.
- Having cancer, a malignancy, or tumor.
- Having an infection.
- Having a major trauma or accident.
- Having surgery.
- Having a chronic disease.
- Having a low socioeconomic status and nutritional deficits.
- Being a black women – white women have a 7 percent chance of anemia whereas black women have a 25 percent chance.
- Being pregnant – iron is lost each day with a net loss over nine months of about 680 mg of elemental iron.
- Giving birth.
- Eating a vegan diet – vegans and vegetarians have a 40 percent chance of being anemic.
- Having heavy periods – menorrhagia, fibroids and other bleeding disorders negatively affect iron status.
- Being on hemodialysis – iron deficiency occurs due to blood loss and poor iron absorption.
- Having celiac disease – half of all celiac disease patients have or will develop anemia.
- Having gastric surgery.
- Using NSAIDs – non-steroidal inflammatory drugs like ibuprofen, aspirin, and naproxen can cause ulcers and bleeding.
- Being obese.
- Having a Helicobacter Pylori infection.
- Having hookworm – some countries frequently see hookworm cases which cause anemia.
- Being an athlete.
To diagnose chronic anemia, a physical examination is conducted, a medical history is taken and risk factors are assessed. Symptoms of an underlying disorder are usually found with an absence of bleeding and the extent of anemia is mild to moderate. Testing may become complex with further testing to ensure diagnostic certainty and rule out other causes. Hematology experts are commonly consulted in diagnosing chronic anemia.
Lab studies include a full blood count including hemoglobin, serum ferritin, and serum soluble transferrin receptor, FBC, peripheral blood smear, reticulocyte count, serum iron, TIBC, transferrin saturation, CRP, ESR, creatinine, LDH, and liver function.
Lab studies commonly indicate:
- normochromic or microcytic hypochromic anemia
- low absolute reticulocyte count
- low serum iron
- low TIBC
- low percent transferrin saturation
- elevated ferritin
Physical findings include:
- Symptoms of fatigue, weakness, shortness of breath, pallor, changes in activity levels or exercise tolerance.
- Symptoms of infection or autoimmune disorder like a stiff neck, joint pain, abdominal or bone pain, rash or hives, and breathing problems.
- Paleness in the eye bed (conjunctival pallor) the palms, palmar creases and nail beds.
Factors not found or likely due to another cause:
- Bleeding – if bleeding is present, a different protocol is initiated. Serum iron, TIBC, iron saturation, and ferritin tests rule out iron deficiency anemia.
- High alcohol intake – alcohol consumption is associated with folate or B12 deficiency.
- Exposure to chemicals, toxins or radiation. Specific and direct questioning about radiation, and chemical exposure is necessary.
- Drug or medication use known to cause anemia.
- Poor nutritional history.
Other Diagnostic Tests
- Bone marrow examination for evaluation of iron stores and bone marrow disorders.
- Renal insufficiency
- Thyroid disease
- Liver disease
- Serum B12 and folate tests for ruling out deficiency.
Diagnosing iron deficient anemia involves a physical examination, a medical history, risk factor assessment and blood tests. Symptoms specific to iron deficiency are commonly found and a systematic search for bleeding is conducted. Symptoms specifically indicating iron deficiency include fatigue and pallor, but also include:
- Pica – a key factor and a craving for non-food items like ice, dirt or paint. About half of iron deficient patients have these abnormal cravings. Cravings are cured with iron replacement.
- Nail changes – about 30 percent have thinning nails, however some other conditions can cause this symptom.
- Hair loss – common symptom.
- Dysphagia – about 10 percent of patients have trouble swallowing.
- Muscular performance deficits – the time that exercise or maximum workload is tolerated decreases. Performance event times are decreased in comparison to normal subjects or previous performance. Performance is restored with iron replacement.
- Mouth and tongue – a burning tongue, bigger or smaller bumps on the tongue, or sores on the mouth commonly occur and are corrected with iron replacement.
- Gastric – gastritis and reduced acid secretion in the stomach.
- Restless legs syndrome – a key factor and common symptom of IDA.
- Lower GI tract irritability, rectal lesions, tumor or hemoroids.
- Growth impairment – infants, children and adolescents may not grow normally.
- Cognitive and behavioral impairment – attention deficits, memory, learning and negative behavioral conditions may sometimes occur.
- Heart failure – severe anemia can cause heart problems which often reverse with iron replacement.
Initial laboratory testing includes:
- Full Blood Count (FBC) (including haemoglobin and haematocrit, platelet count, MCV, MCH, MCHC, red cell distribution width) and peripheral smear.
- Reticulocyte count.
- Iron profile.
Laboratory Blood Results for Iron Deficiency Anemia:
- Serum iron – low
- Total iron-binding capacity (TIBC) – increased
- Transferrin saturation – less than 16%
- Serum ferritin – low and less than 12 nanogram/mL.
Other Diagnostic Tests to determine bleeding:
- Bone marrow biopsy – most accurate test but often not necessary, as it is used mostly for patients who have an unclear blood studies.
- Urine testing – test for blood loss from the renal tract.
- Upper or lower endoscopy – for upper or lower GI symptoms like nausea, burping, constipation or change in bowel habits.
- Rectal exam – insufficiencies or malignancies found in about 1% of patients.
- Celiac disease tests
- Vaginal exam
Anemia Classification and Causes
Normal ranges vary slightly for men and women, and according to age and race. Classification is based on the number of oxygen transporting proteins in the blood:
- Life-threatening anemia: less than 6.5 g/dL
- Severe anemia: less than 8 g/dL
- Mild/moderate anemia: less than 8-11.0 g/dL
- Men older than age 15 years: less than 13 g/dL
- Women older than age 15 years: less than 12 g/dL
- Pregnant women: less than 11 g/dL
- Children 6 months to 5 years: 11 g/dL
- Children 5-11 years: 11.5 g/dL
- Children 12-13 years: 12 g/dL
Causes Found in Chronic Anemia
- chronic kidney disease
- chronic pulmonary disease
- congestive heart failure
- diabetes mellitus
- fungal infections
- giant cell arteritis
- inflammatory bowel disease
- multiple myeloma
- polymyalgia rheumatica
- renal cell carcinoma
- rheumatoid arthritis
- soft tissue infections
Causes Found in Iron-Deficient Anemia
Iron deficiency and iron deficient anemia has four causes:
- Iron intake deficits because of inadequate diet.
- Impaired absorption of iron.
- Iron loss including bleeding, menstruation, blood donation, self-induced bleeding, dialusis and runner’s anemia
- Iron requirements increase due to athletic pursuits, pregnancy, or lactation.
Treatment for Anemia of Chronic Disease (ACD) seeks to improve or cure the underlying disorder or disease. Anemia levels usually correspond to the level or activity of the disease and treating the disease often cures the anemic condition. Treatment of the anemia is sometimes warranted and appropriate. Patients with a disease that cannot be treated and accompanied by non-severe anemia, often do not require aggressive treatment of anemia. Examples of these situations include excision of tumors, remission of malignancies, and recovery after infections. Monitoring and observation of the anemia is practiced in these cases.
Anemia is now understood to be an adaptive physiological condition whereby the body mounts a defense to disease by altering or blocking iron status. Iron circulation decreases in order to stop growth rate of infections, tumors or malignancies. Treatment of the anemia increases iron circulation and decreases the survival rate of the patient. These types of treatment decisions are often left with specialists. Treatment of the disease condition and anemia also depends on availability of treatment, insurance status and other economic factors.
Individual treatment plans will vary. The established protocol for chronic anemia patients does follow an established pattern however:
1/ Treatment of the underlying disease.
2/ Follow with observation of the patient, disease and blood levels.
3/ If the disease does not respond to treatment and/or the anemia continues and poses a risk like pulmonary disease or heart failure, secondary or adjunct treatment like RBC transfusion is initiated. Red blood cell transfusions raise anemia levels to normal. Some people may not be candidates for transfusions because transfusions may pose a risk or are not available. Some people have rare blood types or may have conscientious objections to transfusions. Risks possible with transfusions:
- acute hemolysis with shock
- delayed hemolytic transfusion reaction
- iron overload
- lung injury
- volume overload
- infectious disease transmission
4/ Erythropoiesis-stimulating agents (ESAs) – if transfusions are necessary long-term, ESAs are used alternatively to avoid transfusions. However, iron deficiency must be ruled out first. ESAs stimulate RBC production and are manufactured using recombinant DNA. Risks of ESA treatment are mild but include respiratory or cardiovascular events, tumor growth, and if hemoglobin levels are raised too high (>12 g/dL), the risk of early death increases. Hemoglobin levels are checked monthly, stabilized and treatment is discontinued if necessary, or if no improvement is seen after eight to twelve weeks.
ESAs can be a first option in some conditions:
- chronic kidney disease has a nearly 100 percent response rate.
- Non-myeloid malignancy with chemotherapy treatment.
- HIV treatment with zidovudine.
- Multiple myeloma has an 80% response rate.
Epoetin alfa : 40,000 to 60,000 units subcutaneously once weekly.
Darbepoetin alfa : 200 to 300 micrograms subcutaneously once every 2 weeks.
5/ Supplemental Iron
Elemental iron supplementation may be needed during ESA therapy to increase iron saturation and hemoglobin and achieve an optimal response. Heart failure patients in particular, benefit from iron therapy. Intravenous iron is preferred over oral iron because optimizing ESA is contingent on raising transferring saturation to between 30 to 40 percent. Iron is not given to patients with infection, as iron may promote microorganism growth.
- Sodium ferric gluconate – doses of 62.5 mg intravenously once weekly or once every two weeks. This formula is preferred over iron dextran for less risky negative reactions.
- Iron dextran -dose depends on patient’s blood values and weight but doses are commonly 50 mg intravenously once weekly or 50 mg intravenously once every 2 weeks. A test dose is mandatory as a small number of patients have an anaphylactic reaction. Low molecular -weight iron dextran is preferred over high-molecular weight dextran.
- Sodium ferric gluconate complex : 62.5 mg intravenously once every 2 weeks
- Iron sucrose – doses of 50 mg intravenously once weekly or once every two weeks.
6/ Monitoring – seeks to control blood levels. Scrutiny depends on the nature of the underlying disease and treatment of choice.
Treatment of iron-deficient anemia entails oral iron supplements. Iron is ingested for 3 to 6 months after retesting shows normal iron levels in the blood. Iron is better absorbed with vitamin C and meat. Calcium, fiber, tea, coffee and wine inhibit the absorption of oral iron. Some patients find iron is better tolerated in the intestinal system by taking a lower doses or taking liquid iron.
1/ Oral iron salts commonly used include
- ferrous sulphate : 2-3 mg/kg/day total divided in doses.
- ferrous gluconate : 2-3 mg/kg/day total divided in doses.
- ferrous fumarate : 2-3 mg/kg/day total divided in doses.
2/ Ascorbic acid – Vitamin C is recommended if iron absorption is poor. The dose is 500 mg orally two to three times daily.
3/ Intravenous (Parenteral) Iron – Some patients do not tolerate oral iron and have high volume iron losses and iron must be replaced intravenously.
- Iron dextran – a test dose must be given as some patients experience anaphylactic reactions, an extreme shock to the body. The dose depends on the patient’s blood profile and body weight.
- Ferric gluconate – has a less extreme reaction incidence. The dose is commonly 125 mg intravenously once weekly for 8 weeks.
- Iron sucrose – has similar adverse consequences as iron dextran. The dose is commonly 200 mg/dose five (5) times within a 14-day period.
- Ferumoxytol – used with iron deficiency and kidney disease. The dose is 510 mg intravenously as a single dose given an hour after dialysis.
- Ferric carboxymaltose : the dose depends on patient’s blood profile and body weight.
4/ Treatment failure with oral iron, vitamin C and intravenous iron needs further investigation into causes of bleeding.
5/ Red Cell Transfusion – transfusion is based on a clinical need and co-existing disease factors. Receiving transfusions does not eliminate the need for other iron supplements as transfusion does not raise iron levels significantly. Evidence is emerging that transfusions may be overused. Older, stored blood may have more negative consequences. However, transfusions are commonly used for patients who have chest pain or lightheadedness. Transfusions can improve symptoms and activity tolerance.
6/ Patients who do not respond to treatment and have debilitating symptoms are placed on bed rest.
7/ Monitoring – seeks to control blood levels and depends on the cause of the anemia and treatment of choice. Retesting occurs after 3 to 6 months and yearly afterwards.
Interfering Drugs and Supplements
Some medications and supplements interfere with iron absorption:
- H2-receptor antagonists
- quinolone antibiotics
When the underlying cause of anemia is found and responsive to treatment, anemic conditions improve or resolve. If the anemia does not resolve following successful treatment of a condition, an investigation is necessary to find the second cause of anemia. If blood testing finds restored hemoglobin, an additional six months is needed to restore iron levels. In addition, if anemia is due to nutritional deficits, stopping iron supplements may cause anemia to return.
Iron supplementation – for high risk people including those infants with low socio-economic status, low birth weight babies, pregnant women, those in developing countries, pre-term babies, black, Alaskan and Native American people. Children in high malaria countries are not recommended for iron supplementation. The World Health Organization recommends that all women of childbearing age, even adolescents, if living in a country with a high incidence of anemia, take supplements.
Iron fortified foods are highly preferred and many governments seek to improve their food sources, especially iron fortified milk. Other fortified food includes orange juice and yogurt. Essential fatty acids, iron, zinc, copper, iodine, selenium, vitamins A, D, E, C, B1, B2, B6, and B12, folic acid, niacin and pantothenic acid have all been added to food. Another type of anemia, Vitamin deficiency anemia or megaloblastic anemia is caused by a lack of folic acid and vitamin B12 in the body. Rare cases of anemia have been cured with combinations of iron, certain vital amino acids, and proteins mixed into food. Two strategies for fortification of food:
- Enhance the food sources that are preferred and eaten in quantities. For instance, some countries eat large quantities of wheat, so governments find that enhancing wheat is simple, nutritionally effective, and cost effective.
- Enhance condiments that are preferred and commonly consumed. For instance, fish sauce, curry powder, salt, and sugar have been effectively fortified.
Iron absorption is dependent on the bioavailability of the iron and the other food items eaten at the same time.
- Increases absorption – vitamin C and red meat.
- Decreases absorption – polyphenols in some vegetables, tannins in tea and wine, phytates in bran, and calcium in dairy products.
Vitamin B12 and folic acid supplements are proven useful. Blackstrap molasses is a good source of iron, B vitamins, and minerals. Some herbal supplements are considered to promote health, but generally, a well- balanced diet is enough to prevent iron deficient anemia.
Breastfeeding – is highly encouraged for the first six months of a baby’s life. After that, supplemental foods, especially iron rich foods, can be added but breast feeding should continue until the child is 2 years old. In addition, health advocates recommend that women wait at least 2 years before having another child. Breastfeeding and pregnancy is a negative condition affecting the mother’s health, the baby’s health and the gestating infant’s health.
Preventing Teen Pregnancy – may reduce anemia incidence because pregancy combined with adolescence, places a high demand for iron on both the mother and the child. The mother loses iron during birth and in the postpartum period, which also impacts the child who needs the iron from the mother’s breast milk. The combination of demands of adolescence, pregnancy, birth, postpartum and breastfeeding is particularly troubling to health advocates.
Anemia which occurs due to chemotherapy, trauma, sepsis, malaria, kidney dialysis sometimes do not respond to treatment but may respond to a new class of drugs. Scientists added a corticosteroid and a prolyl hydroxylase inhibitors (PHI) to burst forming unit-erythroids (BFU-Es) which made 300 times more red blood cells. They hope to use these drugs to treat chronic anemia, rare anemia and even hope to use them to reduce steroid use for other conditions.
Another alternative is administration of a drug with the protein Gas6. This protein has been shown to increase sensitivity to recombinant erythropoietin and increase cell signalling. These studies were conducted on mice, however researchers hope to duplicate their studies in humans. In mice, recombinant erythropoietin with the protein Gas6, or with protein Gas6 alone, was successful in treating chronic and acute anemia. The Gas6 protein worked to increase red blood cells to normal levels.
Milk from goats has been found to have similar nutritional profiles as does human milk. Goat milk improves iron status because it aids iron absorption, regenerates hemoglobin, and minimizes the negative effect of calcium on iron absorption. Goat milk has more medium-chain fatty acids that provide good energy and low body fat storage.
Goat milk also provokes less allergic reactions because it contains less casein alpha 1 than cow’s milk. In addition, goat milk has more oligosaccharides that act as prebiotics and promote a good intestinal environment. Researchers consider it an excellent functional food rich in calcium, phosphorous, zinc and selenium. Some countries are using this new information and providing infant formulas made from goat milk.
Researchers at Massachusetts General Hospital (MGH) and Harvard University have developed a mathematical model which can predict who is likely to develop anemia before the anemia occurs. They compressed clinical data into a small program to compare against the general population. The mathematical model simulates young and mature red cells, and how they develop over time. By comparing healthy cell development to common anemia types, they were able to predict the development of iron-deficiency anemia. This model can be very important in finding causes of anemia like colon cancer in the critical window when treatment is effective.
- Urinary Hepcidin – this test can differentiate between iron deficiency anemia and anemia of chronic disease and is being evaluated by researchers.
- Hypochromic erythrocytes – percentages can be calculated manually, in hematology analyzers and is useful in identifying iron deficiency anemia
- Reticulocyte hemoglobin – red cell infants or baby hemoglobin cells decrease within the first few days of IDA. This test is highly sensitive but not widely available yet.
- Erythrocyte Protoporphyrin – immediately precedes hemoglobin and increases when iron in insufficient to form hemoglobin.
- Zinc protoporphyrin – elevated levels are found in iron deficiency anemia and chronic anemia. The test has medium sensitivity and medium to high specificity.
- Soluble transferrin receptor – can be used to differentiate between normal levels of iron and iron deficiency.
- Acute pyelonephritis
- Behcet’s syndrome
- Chronic renal failure
- Community-acquired pneumonia
- Crohn’s disease
- Giant cell arteritis
- Hepatitis A
- Hepatitis B
- Hepatitis C
- HIV infection
- Hodgkin’s lymphoma
- Hospital-acquired pneumonia
- Idiopathic inflammatory myopathies
- Infective endocarditis
- Multiple myeloma
- Non-Hodgkin’s lymphoma
- Polyarteritis nodosa
- Polymyalgia rheumatica
- Pulmonary tuberculosis
- Renal cell carcinoma
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Systemic sclerosis (scleroderma)
- Systemic vasculitis
- Ulcerative colitis
- Urinary tract infections in men
- Urinary tract infections in women
- Wegener’s granulomatosis