That one word carries more impact for a patient than nearly any other term in the medical lexicon. In years past, a diagnosis of leukemia was always associated with a grim prognosis. Even today, when temporary remission can be achieved in a significant number of patients, long-term survival rates (“cure”) are less than impressive. In fact (paradoxically) some of the chemotherapeutic agents used to treat leukemias and other cancers – cyclophosphamide and etoposide, for example – actually increase one’s risk for leukemia.

Leukemias are cancers of white blood cells (WBCs). That may seem a little ironic since WBCs are the guardians of our immune systems, and they’re supposed to protect us from things like cancer. But any cell that can divide is susceptible to the random genetic damage that can lead to malignant transformation.

Since WBCs are found in the bloodstream, the bone marrow, the lymph nodes, the spleen, the liver, and other organs, it isn’t surprising that all of these tissues can be compromised whenever leukemia develops. The manifestations of leukemia arise from suppression of normal blood cell production in the marrow and from organ infiltration by leukemic cells.

Risk Factors for Leukemia

The risk for developing leukemia is increased by a variety of factors:

• Exposure to ionizing radiation (e.g., citizens of Nagasaki and Hiroshima following atom bomb attacks; nuclear “down-winders” in Nevada and southern Utah; patients who have undergone radiotherapy for medical conditions)
• Chemical exposure (benzene, aniline dyes used in hair coloring, pesticides, herbicides)
• Smoking
• Viruses (human T-lymphotropic virus, Epstein-Barr virus)
• Immunodeficiency disorders
• Chromosomal disorders (Down syndrome, Fanconi’s anemia, etc.)
• Age (more than 70% of leukemias occur in individuals over 50)
• Malnutrition (deficiencies of folic acid and vitamins B6 and B12 have been associated with the development of leukemia)

Classification of Leukemias

Originally, leukemias were called “acute” or “chronic” based upon a patient’s life expectancy, but those lines have been blurred somewhat by increased survival times brought about by modern therapies. Nowadays, most experts further categorize leukemias according to the cell types involved and the cells’ level of maturation. Thus, acute leukemias are more likely to be associated with immature, poorly differentiated cells – cells that tend to divide more rapidly, spread more aggressively, and respond poorly to treatment. Chronic leukemias, on the other hand, typically exhibit more mature and better-differentiated cell types.

Leukemias are subdivided into the following cellular types: Acute leukemias are classified as lymphocytic (acute lymphocytic leukemia, or ALL) and myelocytic (acute myelogenous leukemia, or AML) types. Likewise, chronic leukemias are divided into CLL and CML types. Further categorization – useful for determining therapy and prognosis, particularly for acute leukemias – is based upon a FAB (French-American-British) system.

Treatments for Leukemia

Leukemias generally respond to some form of chemotherapy, and a small percentage of patients (around 5%) also undergo radiation treatment. Both forms of treatment are designed to damage the chromosomes of rapidly dividing or otherwise susceptible cells, thereby killing cancer cells without exerting undue damage on normal cells. Unfortunately, these treatments do not distinguish between cancer cells and normal cells that also divide rapidly – blood cells and platelets, the cells lining the gastrointestinal tract, hair follicles, etc. This “spillover” is what creates the harmful side effects of leukemia therapies.

Interferon, a cytokine that influences the immune system, is often used to treat chronic leukemias. Ostensibly, interferon limits the reproduction of leukemia cells while enhancing the immune system’s response to the cancer. Other cytokines have found similar use in treating different forms of leukemia.

Stem cell therapy will probably become an important adjunct for patients who have undergone chemotherapy or radiation to destroy their leukemia cells. Following such conventional treatment, stem cells can be reintroduced to a patient’s bone marrow to replace the destroyed cells and, hopefully, reestablish normal cell lines. This technology is new and carries its own burdens, but stem cells represent a promising modality for cancer therapy.

Growth factors, monoclonal antibody therapies, vaccines, and various immunomodulators are all finding a place in treating leukemias, but many of these modalities are still under investigation. 

This is often the first question that springs to mind whenever someone finds a lump in his or her neck, groin, or armpit. These lumps frequently represent enlarged lymph nodes, which are mistakenly called “glands” by many people.

Lymph nodes are small organs that filter lymph from the various regions of our bodies. Lymph is the fluid that flows between all of our cells and tissues, bathing them with nutrients and vital fluids. Lymph is similar in composition to plasma, which is the liquid component of blood (i.e., what remains when the cells are removed).

Once lymph has circulated through our tissues, most of it returns to the blood vessels, where it mixes with our blood before returning to the heart. A portion of the lymph also enters a separate network of vessels that more or less parallel the blood vessels. At discrete junctions along the course of these lymphatic vessels, lymph nodes act as “sentinels” to capture the lymph, filter it, and analyze it for the presence of infectious organisms, malignant cells, and other unwelcome entities.

White blood cells that reside within the lymph nodes are responsible for mobilizing an immune response to any foreign antigens that might be detected in the lymph. This immune activity usually provokes some degree of inflammation, and inflammation causes the lymph node to swell.

Thus, any stimulus that causes the white cells within a lymph node to react can cause that node to enlarge. Although the proliferation of cancerous cells within a node can certainly cause it to enlarge, cancer is not the most likely reason for lymph node enlargement.

In fact, the potential causes of lymph node enlargement (called lymphadenopathy) are so numerous that even physicians are frequently at a loss to explain why a given node is swollen. When confronted with lymphadenopathy in a patient, many doctors go through a mental checklist to rule out the serious causes and then have the patient return in a few weeks to reevaluate the situation.

Physicians are great fans of mnemonic devices – acronyms that help them to diagnose any number of medical conditions – and this certainly applies to the evaluation of lymphadenopathy.

For example, upon first encountering a patient with an enlarged lymph node (or nodes), most doctors utilize the “ALL AGES” mnemonic: age of the patient; node location; length of time since the node appeared; associated signs and symptoms (fever, weight loss, night sweats, etc.); generalized vs. localized lymphadenopathy; extranodal associations (i.e., are there obvious causes for the nodal enlargement?); is the patient’s spleen enlarged?

This ALL AGES approach helps a doctor to decide whether watchful waiting is appropriate or if a more aggressive evaluation – including, perhaps, biopsy of the lymph node – is merited.

In addition, during their examination of a patient with an enlarged node, physicians use a CHICAGO mnemonic (see below) to guide their thoughts and direct their recommendations for future management. In the overwhelming majority of cases, the ALL AGES and CHICAGO approaches reveal benign causes for the lymphadenopathy.

The CHICAGO mnemonic outlines the plethora of specific conditions that are associated with lymphadenopathy:

Cancers (again, a relatively rare cause of lymphadenopathy): Hodgkin’s disease; non-Hodgkin’s lymphoma; leukemia; multiple myeloma; Waldenström macroglobulinemia; mastocytosis; metastatic breast, prostate, lung, renal, or other tumors

Hypersensitivity (allergy-like) syndromes: drug reactions (Dilantin, indomethacin, gold, allopurinol, carbamazepine, sulfa drugs, etc.); serum sickness; silicone or collagen reaction; vaccination reaction; graft-vs-host disease (found in transplant patients)

Infections: a long list that includes bacteria (staph, strep, cat-scratch fever, tuberculosis, syphilis, etc.); viruses (mononucleosis, hepatitis, cytomegalovirus, colds, herpes, HIV, chickenpox, rubella, etc.); chlamydia; protozoa (toxoplasmosis); rickettsia (scrub typhus, tick fevers, etc.); helminths (subcutaneous or lymphatic worm infestations)

Connective tissue diseases: lupus; dermatomyositis; mixed connective tissue disease; Sjögren’s syndrome, rheumatoid arthritis, etc.

Atypical lymphoproliferative disorders (a term meaning “unusual diseases that cause lymph nodes to get bigger”; it helps to put the “A” in CHICAGO): Castleman disease; angioimmunoblastic lymphadenopathy; lymphomatoid granulomatosis; Wegener’s granulomatosis; etc.

Granulomatosis disorders: tuberculosis and other mycobacterial infections; cat-scratch fever; berylliosis; histoplasmosis; sarcoidosis, etc.

Others: inflammatory pseudotumor of lymph nodes; histiocytic necrotizing lymphadenitis; sinus histiocytosis; vascular disorders, etc.

People who are not physicians may not know all of the fancy terminology, but they can use a similar systematic approach to lymphadenopathy. When confronted with an enlarged lymph node, it helps to remember that lymph drains from our extremities toward our heart, just like our blood does. Thus, if a node in the neck is swollen, it might be reacting to an infection or injury on the scalp, in the ear, or in the throat. Likewise, a swollen node in the groin or armpit might reflect an inflammatory process of the leg or arm, respectively. A careful search of the anatomy “upstream” from an enlarged node often reveals a simple explanation for the node’s behavior; such self-examination can be reassuring…and save the cost and anxiety of an unnecessary doctor visit.

Finally, it always helps to remember that once a lymph node swells in response to an inflammatory stimulus, it can remain swollen for many days, or even weeks. Tender, mobile, spongy nodes are much more likely to be inflammatory (that is, benign) than are nontender, fixed, and firm nodes. The latter merit a doctor’s attention – as does any swollen node that doesn’t resolve within three to four weeks or that continues to enlarge when there’s no apparent reason for it to do so. 

Allergic rhinitis is a true atopic condition: it is driven by an exaggerated IgE-mediated immune response (a type I hypersensitivity reaction, for those who keep track of such things). Whenever the appropriate foreign antigen binds to IgE, and thence to IgE receptors on the mast cells of susceptible persons, the mast cells release copious amounts of histamine, which is a molecule that dilates blood vessels, increases capillary permeability, triggers neuronal reflexes, increases salivary and mucoid secretions, and constricts smooth muscles in the airways.

Thus, histamine’s effects on various tissues are responsible for all of the signs and symptoms that we normally associate with hay fever.

Allergic rhinitis is typically caused by exposure to tree pollens in the spring, grass and weed pollens in summertime, and weed pollens in autumn. Fungal spores can also trigger symptoms of allergic rhinitis. The instigator of a given individual’s symptoms will vary according to that person’s specific sensitivities, the region where he or she lives, and the time of year.

Perennial rhinitis, which affects some unfortunate individuals on a year-round basis, is usually caused by ongoing exposure to indoor antigens (dust mites, mold spores, pet dander, etc.) or sensitivity to plants that pollinate in a sequential fashion – or a combination of these factors.

Allergic rhinitis often coexists with other allergic conditions, such as atopic dermatitis or asthma. In the case of the latter, it isn’t clear whether asthma and allergic rhinitis are both simultaneously triggered by the same agent, or if rhinitis serves to trigger bronchospasm, with its attendant signs and symptoms.

Diagnosis of allergic rhinitis is usually straightforward: a person’s history, clinical signs, and response to empiric antihistamine treatment will tell the tale. However, if a patient doesn’t improve with antihistamines – or if desensitization therapy is planned – skin tests can clarify sensitivities to specific allergens (cockroach, dust mite, cat, dog, horse, mold, hay, etc.).

If a symptomatic person’s skin tests are negative – that is, they reveal no sensitivity to any of the tested allergens – then he or she may be suffering from a non-allergic form of rhinitis: vasomotor, gustatory, drug-induced, hormonal, or infectious rhinitis; or a special form of rhinitis called “non-allergic rhinitis with eosinophilia (NARES).”

Treatment of allergic rhinitis is aimed at alleviating symptoms and, whenever possible, reducing exposure to offending allergens. Eliminating some sources of allergens may be possible (removing pets from the home, for example); usually, though, exposure-reducing measures are designed to merely limit the allergen load: keeping lawns mowed so they don’t pollinate; eliminating weeds around one’s home; placing mite-proof covers on mattresses and pillows; fumigating for roaches; frequent vacuuming, using vacuum cleaners that employ HEPA filters, etc.

Oral antihistamines and decongestants often furnish sufficient relief for individuals whose symptoms are limited to a few weeks of the year. Nasal corticosteroid or mast-cell-stabilizing sprays are frequently added to oral therapies. Nasal saline drops or sprays are useful adjuncts to any therapy; by helping to loosen thickened mucous and moisten nasal membranes, this inexpensive modality can significantly alleviate symptoms.

Montelukast (Singulair) and zafirlukast (Accolate), medications that interfere with the activity of leukotrienes (yet another inflammatory molecule), have proven beneficial for some people.

When symptoms are severe or prolonged, desensitization therapy may be useful. Following skin tests to determine a patient’s specific sensitivities, an injectable serum is formulated and administered beneath the skin in gradually increasing doses. The idea behind this therapy – some would say it is homeopathic in its approach – is to initially expose the immune system to tiny amounts of an allergen and gradually increase that exposure in an effort to “fool” the immune system into accepting the allergen. Actually, the reasoning behind such therapy is sound: incremental doses of an allergen may induce the production of different classes of antibodies (IgG, for example) that will bind the allergen before it can attach to the IgE that leads to mast cell degranulation and histamine release. This approach may also encourage the production of cytokines or white cells that inhibit the allergic response.

Whatever treatment is eventually brought to bear on an individual basis, anyone who has ever suffered from hay fever will probably acknowledge that no treatment is 100% effective.

Indeed, most allergic rhinitis sufferers will admit that they can’t wait until their season of personal travail has passed and they can get on with their lives…until next year.

IgA deficiency is the most common primary immunodeficiency found in humans, affecting about one in every 300 people. This disorder is transmitted as an autosomal dominant trait with incomplete penetrance; thus, everyone who acquires the gene will exhibit some form of the disease, but some will have much milder symptoms than others.

While some individuals affected by IgA deficiency are nearly asymptomatic – and some even remit spontaneously – others develop recurrent respiratory infections (sinusitis, otitis, pneumonia, etc.), diarrhea, or urinary tract infections. Many sufferers are troubled by chronic allergies, and a significant number of patients with IgA deficiency develop autoimmune illnesses. Indeed, in such cases, the autoimmune condition can become more troublesome than the primary immune deficiency and lead to early mortality.

Interestingly, individuals with IgA deficiency can develop antibodies that are directed against IgA (these antibodies would obviously come from other classes, namely IgG, IgM, or IgE). This typically occurs when IgA-deficient persons receive blood products or immune globulins that contain small amounts of IgA; since the IgA is a novel antigen (from the IgA-deficient patient’s point of view), the normal immune response is triggered, and anti-IgA antibodies are formed to reject the “foreign” invader. When the individual is exposed to even minute amounts of IgA in the future, a life-threatening anaphylactic reaction can ensue.

Therefore, if a person with IgA deficiency requires a blood transfusion, he or she should only receive washed red blood cells or frozen blood that has had all extraneous antibodies removed. Additionally, intravenous immunoglobulins should never be administered to people with IgA deficiency. These individuals should wear identification bracelets that alert medical personnel to their condition to prevent the inadvertent administration of IgA-containing blood products.

IgA-deficient individuals who develop autoimmune disorders (lupus, celiac disease, autoimmune hepatitis, Crohn’s disease, ulcerative colitis, etc.) are treated accordingly. Antibiotics and infection control precautions (frequent hand washing, avoidance of crowds, immunizations, prudent travel habits, etc.) are the keystones of treatment for those who are troubled by recurrent infections.

Vitamin D exerts its effects by binding to a nuclear receptor that is present in many of our cells. This vitamin D receptor (VDR) regulates the activity of at least 50 human genes, some of which are responsible for optimal immune activity.

T cells and antigen-presenting cells (macrophages, dendritic cells, etc.) express the vitamin D receptor; some macrophages also possess the enzyme that converts 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D (the vitamin’s active form). VDR-dependent stimulation of immune cells promotes a variety of cellular functions: antigen processing, cytokine production, cellular differentiation and division, production of antimicrobial peptides, and antibody production are all influenced by vitamin D.

Additionally, vitamin D exerts a suppressive effect on cellular division while simultaneously encouraging cellular differentiation in many tissues. These two activities help to prevent the proliferation of undifferentiated cells – in other words, vitamin D helps to inhibit the development of cancers. Epidemiologic surveys have demonstrated a strong link between low serum levels of vitamin D and cancers of the colon, breast, prostate and skin.

Because vitamin D helps to control immune-mediated inflammation, it may also inhibit those processes that lead to autoimmunity. Deficiency of vitamin D has been linked to several autoimmune diseases, including Sjögren’s syndrome, Crohn’s disease, multiple sclerosis, rheumatoid arthritis, and thyroiditis. Interestingly, vitamin D deficiency has been misdiagnosed as chronic fatigue, fibromyalgia, and peripheral neuropathy.

It should be noted that vitamin D appears to be a selective immune modulator—that is, not all immune-mediated conditions are positively affected by supplementation, because not all immune problems are related to vitamin D deficiency. Scientists are helping to unravel some of vitamin D’s immunologic functions, but research in this area is just beginning.

Current recommendations for daily allowances of vitamin D (400 IU for adults) are probably on the low side, particularly since this nutrient is not found in abundance in many foods. 20 minutes of exposure to sunlight every day will confer adequate vitamin D production, but many people wish to avoid sunlight – along with its risks for skin cancer and solar elastosis – and adequate exposure is difficult for people who work indoors or who live at higher latitudes. Hence, for many individuals supplementation is the key to avoiding deficiency. Total doses should not exceed 2,000 IU daily, and vitamin D3 (cholecalciferol) has been shown to be more effective than D2 (ergocalciferol) in humans.

Simply taking a vitamin D supplement, however, is not sufficient to reap its full benefits. Adequate intake of calcium (1200 – 1500 mg daily) and magnesium (500 – 600 mg daily) is necessary to help vitamin D perform optimally. Phosphorus is also important, but this mineral is present in adequate amounts in the typical American diet. Chelated forms of minerals – those that are “hooked” to an amino acid – are usually better absorbed than the more commonly used (and cheaper) supplements on the market.