Screening for Immunologic Disease

Chapter 12


Screening for Immunologic Disease


Immunology, one of the few disciplines with a full range of involvement in all aspects of health and disease, is one of the most rapidly expanding fields in medicine today. Staying current is difficult at best, considering the volume of new immunologic information generated by clinical researchers each year. The information presented here is a simplistic representation of the immune system, with the main focus on screening for immune-induced signs and symptoms mimicking neuromuscular or musculoskeletal dysfunction.


Immunity denotes protection against infectious organisms. The immune system is a complex network of specialized organs and cells that has evolved to defend the body against attacks by “foreign” invaders. Immunity is provided by lymphoid cells residing in the immune system. This system consists of central and peripheral lymphoid organs (Fig. 12-1).



By circulating its component cells and substances, the immune system maintains an early warning system against both exogenous microorganisms (infections produced by bacteria, viruses, parasites, and fungi) and endogenous cells that have become neoplastic.


Immunologic responses in humans can be divided into two broad categories: humoral immunity, which takes place in the body fluids (extracellular) and is concerned with antibody and complement activities, and cell-mediated or cellular immunity, primarily intracellular, which involves a variety of activities designed to destroy or at least contain cells that are recognized by the body as being alien and harmful. Both types of responses are initiated by lymphocytes and are discussed in the context of lymphocytic function.



Using the Screening Model


As always in the screening evaluation of any client, the medical history is the most important variable, followed by any red flags in the clinical presentation and an assessment of associated signs and symptoms. Many immune system disorders have a unique chronology or sequence of events that define them. When the immune system may be involved, some important questions to ask include the following:




Past Medical History


As mentioned, the family history is important when assessing the role of the immune system in presenting signs and symptoms. Persons with fibromyalgia or chronic pain often have a family history of alcoholism, depression, migraine headaches, gastrointestinal (GI) disorders, or panic attacks.


Clients with systemic inflammatory disorders may have a family history of an identical or related disorder such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), autoimmune thyroid disease, multiple sclerosis (MS), or myasthenia gravis (MG). Other rheumatic diseases that are often genetically linked include seronegative spondyloarthropathy.


The seronegative spondyloarthropathies include a wide range of diseases linked by common characteristics such as inflammatory spine involvement (e.g., sacroiliitis, spondylitis), asymmetric peripheral arthritis, enthesopathy, inflammatory eye disease, and musculoskeletal and cutaneous features. All of these changes occur in the absence of serum rheumatoid factor (RF), which is present in about 85% of people with RA.1


This group of diseases includes ankylosing spondylitis (AS), reactive arthritis (ReA; such as Reiter’s syndrome), psoriatic arthritis (PsA), and arthritis associated with inflammatory bowel disease (IBD; such as Crohn’s disease or ulcerative colitis).


A recent history of surgery may be indicative of bacterial or reactive arthritis, which requires immediate medical evaluation.




Clinical Presentation


Symptoms of rheumatic disorders often include soft tissue and/or joint pain, stiffness, swelling, weakness, constitutional symptoms, Raynaud’s phenomenon, and sleep disturbances. Inflammatory disorders, such as RA and polymyalgia rheumatica (PMR), are marked by prolonged stiffness in the morning lasting more than 1 hour. This stiffness is relieved with activity, but it recurs after the person sits down and subsequently attempts to resume activity. This is referred to as the gel phenomenon.


Specific arthropathies have a predilection for involving specific joint areas. For example, involvement of the wrists and proximal small joints of the hands and feet is a typical feature of RA. RA tends to involve joint groups symmetrically, whereas the seronegative spondyloarthropathies tend to be asymmetric. PsA often involves the distal joints of the hands and feet.1


In anyone with swelling, especially single-joint swelling, it is necessary to distinguish whether this swelling is articular (as in arthritis), is periarticular (as in tenosynovitis), involves an entire limb (as with lymphedema), or occurs in another area (such as with lipoma or palpable tumors). The therapist will need to assess whether the swelling is intermittent, persistent, symmetric, or asymmetric and whether the swelling is minimal in the morning but worse during the day (as with dependent edema).


Generalized weakness is a common symptom of individuals with immune system disorders in the absence of muscle disease. If the weakness involves one limb without evidence of weakness elsewhere, a neurologic disorder may be present. Anyone having trouble performing tasks with the arms raised above the head, difficulty climbing stairs, or problems arising from a low chair may have muscle disease.


Nail bed changes are especially indicative of underlying inflammatory disease. For example, small infarctions or splinter hemorrhages (see Fig. 4-34) occur in endocarditis and systemic vasculitis. Characteristics of systemic sclerosis and limited scleroderma include atrophy of the fingertips, calcific nodules, digital cyanosis, and sclerodactyly (tightening of the skin). Dystrophic nail changes are characteristic of psoriasis. Spongy synovial thickening or bony hypertrophic changes (Bouchard’s nodes) are present with RA and other hand deformities.





Immune System Pathophysiology


Immune disorders involve dysfunction of the immune response mechanism, causing overresponsiveness or blocked, misdirected, or limited responsiveness to antigens. These disorders may result from an unknown cause, developmental defect, infection, malignancy, trauma, metabolic disorder, or drug use. Immunologic disorders may be classified as one of the following:




Immunodeficiency Disorders


When the immune system is underactive or hypoactive, it is referred to as being immunodeficient or immunocompromised such as occurs in the case of anyone undergoing chemotherapy for cancer or taking immunosuppressive drugs after organ transplantation.



Acquired Immunodeficiency Syndrome


Human immunodeficiency virus (HIV) is a cytopathogenic virus that causes acquired immunodeficiency syndrome (AIDS). HIV has been identified as the causative agent, its genes have been mapped and analyzed, drugs that act against it have been found and tested, and vaccines against the HIV infection have been under development.


Acquired refers to the fact that the disease is not inherited or genetic but develops as a result of a virus. Immuno refers to the body’s immunologic system, and deficiency indicates that the immune system is underfunctioning, resulting in a group of signs or symptoms that occur together called a syndrome.


People who are HIV-infected are vulnerable to serious illnesses called opportunistic infections or diseases, so named because they use the opportunity of lowered resistance to infect and destroy. These infections and diseases would not be a threat to most individuals whose immune systems functioned normally. Pneumocystis carinii pneumonia (PCP) continues to be a major cause of morbidity and mortality in the AIDS population.


HIV infection is the fifth leading cause of death for people who are between 25 and 44 years old in the United States. Each year, about 2 million people worldwide die of AIDS. African Americans represent about 12% of the total US population but makeup over half of all AIDS cases reported. AIDS is the leading cause of death for African-American men between the ages of 35 and 44. Overall estimates are that 850,000 to 950,000 US residents are living with HIV infection, one-quarter of whom are unaware of their infection. Approximately 56,000 new HIV infections occur each year in the United States, and approximately 2.7 million new HIV cases occur each year worldwide (Box 12-1).2



BOX 12-1   Overview of Aids in the United States


What it is: AIDS (acquired immunodeficiency syndrome) is a contagious disease that destroys the T cells, a key component of the body’s immune system.


What causes it: AIDS is caused by the human immunodeficiency virus (HIV), spread through sexual contact, needles, or syringes shared by injection drug users (IDUs); transfusion of infected blood or blood products; or perinatal transmission (from infected birthing or breast-feeding mother to her infant).


Who gets it: Primary persons infected with HIV have been homosexual men (men who have sex with men [MSM] and MSMs who have sex with women) and IDUs. The Centers for Disease Control and Prevention (CDC) estimate that heterosexual contact is responsible for 3% of male cases and 34% of female cases. Although 1 million Americans are infected, one-fourth do not know they have it; as many as one-third of adults tested never come back for the results.105


Diagnosis: Screening for AIDS is conducted by testing a fingerstick sample of blood for the presence of antibodies to HIV-1. The test indicates only if a person has been exposed to the virus. A new “quick” test called OraQuick Rapid HIV Antibody Test is almost 100% accurate, and results are available within 20 minutes. A positive test requires additional confirmation testing.


Prognosis: At present, there is no cure, but many people in the United States remain healthy and active with combination antiretroviral medications designed to attack HIV in various stages of its life cycle; when death occurs, it is usually as a result of “opportunistic” infections or cancers that the immunosuppressed body cannot resist. IDUs are four times more likely to die of AIDS than individuals infected through sexual contact.106



Risk Factors: Population groups at greatest risk include commercial sex workers (prostitutes) and their clients, men having sex with men, injection drug users (IDUs), blood recipients, dialysis recipients, organ transplant recipients, fetuses of HIV-infected mothers or babies being breast-fed by an HIV-infected mother, and people with sexually transmitted diseases (STDs). The latter group is estimated to have a 3 to 5 times higher risk for HIV infection compared with those having no STDs.


The rate of new cases of HIV among bisexual men of all races has started to rise again after a period of relative stability. Experts suggest the increase is due to erosion of safe sex practices referred to as prevention fatigue. African Americans (both men and women) are still 8 times as likely as whites to contract HIV, although the rate of newly diagnosed HIV infections among African Americans is slowly declining.3



Transmission: Transmission of HIV occurs according to the following descending hierarchy4:



Transmission occurs through horizontal transmission (from either sexual contact or parenteral exposure to blood and blood products) or through vertical transmission (from HIV-infected mother to infant). HIV is not transmitted through casual contact, such as the shared use of food, towels, cups, razors, or toothbrushes, or even by kissing. Despite substantial advances in the treatment of HIV, the number of new infections has not decreased in the past 10 years. Prevention of infection transmission by reduction of behaviors that might transmit HIV to others is critical.5


Transmission always involves exposure to some body fluid from an infected client. The greatest concentrations of virus have been found in blood, semen, cerebrospinal fluid, and cervical/vaginal secretions. HIV has been found in low concentrations in tears, saliva, and urine, but no cases have been transmitted by these routes. Breast-feeding is a route of HIV transmission from an HIV-infected mother to her infant. The reduction of HIV transmission through breast milk remains a challenge in many resource-poor settings.6,7


Any injectable drug, legal or illegal, can be associated with HIV transmission. It is not injection drug use that spreads HIV but the sharing of HIV-infected intravenous (IV) drug needles among individuals. Despite the perception that only IV injection is dangerous, HIV also can be transmitted through subcutaneous and intramuscular injection. Use of needles contaminated with blood for tattooing or body piercing are included in this category.


Public health organizations have changed their terminology, substituting the abbreviation IDU (injection drug user) for the earlier term IVDU (IV drug user). IDUs who sterilize their drug paraphernalia with a 1 : 10 solution of bleach to water before passing the needles are less likely to spread HIV. For further information regarding this or other HIV/AIDS-related questions, contact the CDC-INFO (formerly the CDC National AIDS Hotline) 24 hours/day, 7 days a week, at 1-800-CDC-INFO (1-800-232-4636).



Blood and Blood Products: Parenteral transmission occurs when there is direct blood-to-blood contact with a client infected with HIV. This can occur through sharing of contaminated needles and drug paraphernalia (“works”), through transfusion of blood or blood products, by accidental needlestick injury to a health care worker, or from blood exposure to nonintact skin or mucous membranes. Health care workers who have contact with clients with AIDS and who follow routine instructions for self-protection are a very low risk group.


Almost all persons with hemophilia born before 1985 have been infected with HIV. Heat-treated factor concentrates, involving a method of chemical and physical processes that completely inactivate HIV, became available in 1985, effectively eliminating the transmission of HIV to anyone with a clotting disorder who is receiving blood or blood products.


The risk for acquiring HIV infection through blood transfusion today is estimated conservatively to be one in 1.5 million, based on 2007-2008 data.8 A blood center in Missouri discovered that blood components from a donation in November 2008 tested positive for HIV infection.9 A subsequent investigation determined that the blood donor had last donated in June 2008, at which time he incorrectly reported no HIV risk factors and his donation tested negative for the presence of HIV. One of the two recipients of blood components from this donation, an individual undergoing kidney transplantation, was found to be HIV infected, and an investigation determined that the recipient’s infection was acquired from the donor’s blood products. The CDC advises that even though such transmissions are rare, health care providers should consider the possibility of transfusion-transmitted HIV in HIV-infected transfusion recipients with no other risk factors.10


Additionally, HIV has been transmitted heterosexually from infected men with hemophilia to spouses or sexual partners in what is termed the second wave of infection and on to children born to infected couples. HIV infection in the United States is currently on the increase among women exposed via sexual intercourse with HIV-infected men. Minority women and women over the age of 50 are being affected more frequently than in prior years.11



Clinical Signs and Symptoms: Many individuals with HIV infection remain asymptomatic for years, with a mean time of approximately 10 years between exposure and development of AIDS. Systemic complaints, such as weight loss, fevers, and night sweats, are common. Cough or shortness of breath may occur with HIV-related pulmonary disease. GI complaints include changes in bowel function, especially diarrhea.


Cutaneous complaints are common and include dry skin, new rashes, and nail bed changes. Because virtually all of these findings may be seen with other diseases, a combination of complaints is more suggestive of HIV infection than any one symptom.


Many persons with AIDS experience back pain, but the underlying causes may differ. Decrease in muscle mass with subsequent postural changes may occur as a result of the disease process or in response to medications. It is not uncommon for pain to develop in the back or another musculoskeletal location where there may have been a previous injury. This is more likely to occur when the T-cell count drops.


Bone disorders such as osteopenia, osteoporosis, and osteonecrosis have been reported in association with HIV, but the etiology and mechanism of these disorders are unknown. Prevalence reported varies from study to study; scientists are researching the influence of antiretroviral therapy and lipodystrophy (absence or presence), severity of HIV disease, and overlapping risk factors for bone loss (e.g., smoking and alcohol intake). The therapist should conduct a risk factor assessment for bone loss in anyone with known HIV and educate clients about prevention strategies.12


Any woman at risk for AIDS should be aware of the possibility that recurrent or stubborn cases of vaginal candidiasis may be an early sign of infection with HIV. Pregnancy, diabetes, oral contraceptives, and antibiotics are more commonly linked to these fungal infections.



Side Effects of Medication: The therapist should review the potential side effects from medication used in the treatment of AIDS. Delayed toxicity with long-term treatment for HIV-1 infection with antiretroviral therapy occurs in a substantial number of affected individuals.13–15 The more commonly occurring symptoms include rash, nausea, headaches, dizziness, muscle pain, weakness, fatigue, and insomnia. Hepatotoxicity is a common complication; the therapist should be alert for carpal tunnel syndrome, liver palms, asterixis, and other signs of liver impairment (see Chapter 9).


Body fat redistribution to the abdomen, upper body, and breasts occurs as part of a condition called lipodystrophy associated with antiretroviral therapy. Other metabolic abnormalities, such as dysregulation of glucose metabolism (e.g., insulin resistance, diabetes), combined with lipodystrophy are labeled lipodystrophic syndrome (LDS). LDS contributes to problems with body image and increases the risk for cardiovascular complications.16–19



Clinical Signs and Symptoms




Advanced Symptomatic HIV Infection




AIDS and Other Diseases


AIDS is a unique disease—no other known infectious disease causes its damage through a direct attack on the human immune system. Because the immune system is the final mediator of human host–infectious agent interactions, it was anticipated early that HIV infection would complicate the course of other serious human diseases.


This has proved to be the case, particularly for TB and certain sexually transmitted infections such as syphilis and the genital herpes virus. Cancer has been linked with AIDS since 1981; this link was discovered with the increased appearance of a highly unusual malignancy, Kaposi’s sarcoma. Since then, HIV infection has been associated with other malignancies, including non-Hodgkin’s lymphoma (NHL), AIDS-related primary central nervous system lymphoma, and hepatocellular carcinoma.20–22



Kaposi’s Sarcoma: Classic Kaposi’s sarcoma (KS) was first recognized as a malignant tumor of the inner walls of the heart, veins, and arteries in 1873 in Vienna, Austria. Before the AIDS epidemic, KS was a rare tumor that primarily affected older people of Mediterranean and Jewish origin.


Clinically, KS in HIV-infected immunodeficient persons occurs more often as purplish-red lesions of the feet, trunk, and head (Fig. 12-2). The lesion is not painful or contagious. It can be flat or raised and over time frequently progresses to a nodule. The mouth and many internal organs (especially those of the GI and respiratory tracts) may be involved either symptomatically or subclinically.



Prognosis depends on the status of the individual’s immune system. People who die of AIDS usually succumb to opportunistic infections rather than to KS.




Tuberculosis: Tuberculosis (TB) was considered a stable, endemic health problem, but now, in association with the HIV/AIDS pandemic, TB is resurgent.23 The recent emergence of multiple-drug–resistant TB, which has reached epidemic proportions in New York City, has created a serious and growing threat to the capacity of TB control programs (see Chapter 7).


In urban areas of the United States, the present upsurge in TB cases is occurring among young (aged 25 to 44 years) IDUs, ethnic minorities, prisoners and prison staff (because of poorly ventilated and overcrowded prison systems), homeless people, and immigrants from countries with a high prevalence of TB.


The first major interaction between HIV and TB occurs as a result of the weakening of the immune system in association with progressive HIV infection. The great majority of individuals exposed to TB are infected but not clinically ill. Their subclinical TB infection is kept in check by an active, healthy immune system. However, when a TB-infected person becomes infected with HIV, the immune system begins to decline, and at a certain level of immune damage from HIV, the TB bacteria become active, causing clinical pulmonary TB.


TB is the only opportunistic infection associated with AIDS/HIV that is directly transmissible to household and other contacts. Therefore each individual case of active TB is a threat to community health.




HIV Neurologic Disease: HIV neurologic disease may be the presenting symptom of HIV infection and can involve the central and peripheral nervous systems. HIV is a neurotropic virus and can affect neurologic tissues from the initial stages of infection. In the early course of the infection, the virus can cause demyelination of central and peripheral nervous system tissues.24 Signs and symptoms range from mild sensory polyneuropathy to seizures, hemiparesis, paraplegia, and dementia.



Central Nervous System: Central nervous system (CNS) disease in HIV-infected clients can be divided into intracerebral space–occupying lesions, encephalopathy, meningitis, and spinal cord processes. Toxoplasmosis is the most common space–occupying lesion in HIV-infected clients. Presenting symptoms may include headache, focal neurologic deficits, seizures, or altered mental status.


AIDS dementia complex (HIV encephalopathy) is the most common neurologic complication and the most common cause of mental status changes in HIV-infected clients. It is characterized by cognitive, motor, and behavioral dysfunction. This disorder is similar to Alzheimer’s dementia but has less impact on memory loss and a greater effect on time-related skills (i.e., psychomotor skills learned over time such as playing piano or reading).


Early symptoms of AIDS dementia involve difficulty with concentration and memory, personality changes, irritability, and apathy. Depression and withdrawal occur as the dementia progresses. Motor dysfunction may accompany cognitive changes and may result in poor balance, poor coordination, and frequent falls.


Progressive multifocal leukoencephalopathy (PML), which produces localized lesions within the brain, causes demyelination in the brain and leads to death within a few months.


In addition to the brain, neurologic disorders related to AIDS and HIV may affect the spinal cord, appearing as myelopathies. A vacuolar myelopathy often appears in the thoracic spine and causes gradual weakness, painless gait disturbance characterized by spasticity, and ataxia in the lower extremities that progresses to include weakness of the upper extremities.


Structural and inflammatory abnormalities in the muscles of people with HIV have been reported to impair the muscle’s ability to extract or utilize oxygen during exercise. Clinical manifestations of HIV-associated myopathies include proximal weakness, myalgia, abnormal electromyogram (EMG) activity, elevated creatine kinase, and decreased functioning of the muscle.25



Peripheral Nervous System: Peripheral nerve disease is a common complication of the HIV infection. Peripheral nervous system syndromes include inflammatory polyneuropathies, sensory neuropathies, and mononeuropathies. An inflammatory demyelinating polyneuropathy similar to Guillain-Barré syndrome can occur in HIV-infected clients. Cytomegalovirus (CMV), a highly host-specific herpes virus that infects the nerve roots, may result in an ascending polyradiculopathy characterized by lower extremity weakness progressing to flaccid paralysis.


The most common neuropathy develops into painful sensory neuropathy with numbness and burning or tingling in the feet, legs, or hands. Immobility caused by painful neuropathies can result in deconditioning and eventual cardiopulmonary decline.



Clinical Signs and Symptoms


HIV Neurologic Disease





Hypersensitivity Disorders


Although the immune system protects the body from harmful invaders, an overactive or overzealous response is detrimental. When the immune system becomes overactive or hyperactive, a state of hypersensitivity exists, leading to immunologic diseases such as allergies.


Although the word allergy is widely used, the term hypersensitivity is more appropriate. Hypersensitivity designates an increased immune response to the presence of an antigen (referred to as an allergen) that results in tissue destruction.


The two general categories of hypersensitivity reaction are immediate and delayed. These designations are based on the rapidity of the immune response. In addition to these two categories, hypersensitivity reactions are divided into four main types (I to IV).



Type I Anaphylactic Hypersensitivity (“Allergies”)



Allergy and Atopy: Allergy refers to the abnormal hypersensitivity that takes place when a foreign substance (allergen) is introduced into the body of a person likely to have allergies. The body fights these invaders by producing the special antibody immunoglobulin E (IgE). This antibody (now a vital diagnostic sign of many allergies), when released into the blood, breaks down mast cells, which contain chemical mediators, such as histamine, that cause dilation of blood vessels and the characteristic symptoms of allergy.


Atopy differs from allergy because it refers to a genetic predisposition to produce large quantities of IgE, causing this state of clinical hypersensitivity. The reaction between the allergen and the susceptible person (i.e., allergy-prone host) results in the development of a number of typical signs and symptoms usually involving the GI tract, respiratory tract, or skin.




Anaphylaxis: Anaphylaxis, the most dramatic and devastating form of type I hypersensitivity, is the systemic manifestation of immediate hypersensitivity. The implicated antigen is often introduced parenterally such as by injection of penicillin or a bee sting. The activation and breakdown of mast cells systematically cause vasodilation and increased capillary permeability, which promote fluid loss into the interstitial space, resulting in the clinical picture of bronchospasms, urticaria (wheals or hives), and anaphylactic shock.


Initial manifestations of anaphylaxis may include local itching, edema, and sneezing. These seemingly innocuous problems are followed in minutes by wheezing, dyspnea, cyanosis, and circulatory shock. Clinical signs and symptoms of anaphylaxis are listed by system in Table 12-1.



Clients with previous anaphylactic reactions (and the specific signs and symptoms of that individual’s reaction) should be identified by using the Family/Personal History form. Identification information should be worn at all times by individuals who have had previous anaphylactic reactions. For identified and unidentified clients, immediate action is required when the person has a severe reaction. In such situations, the therapist is advised to call for emergency assistance.



Type II Hypersensitivity (Cytolytic or Cytotoxic)


A type II hypersensitivity reaction is caused by the production of autoantibodies against self cells or tissues that have some form of foreign protein attached to them. The autoantibody binds to the altered self cell, and the complex is destroyed by the immune system. Typical examples of this type of hypersensitivity are hemolytic anemias, idiopathic thrombocytopenic purpura (ITP), hemolytic disease of the newborn, and transfusion of incompatible blood. Blood group incompatibility causes cell lysis, which results in a hemolytic transfusion reaction. The antigen responsible for initiating the reaction is a part of the donor red blood cell (RBC) membrane.


Manifestations of a transfusion reaction result from intravascular hemolysis of RBCs.



Clinical Signs and Symptoms


Type II Hypersensitivity





Type III Hypersensitivity (Immune Complex)


Immune complex disease results from formation or deposition of antigen-antibody complexes in tissues. For example, the antigen-antibody complexes may form in the joint space, with resultant synovitis, as in RA. Antigen-antibody complexes are formed in the bloodstream and become trapped in capillaries or are deposited in vessel walls, affecting the skin (urticaria), the kidneys (nephritis), the pleura (pleuritis), and the pericardium (pericarditis).


Serum sickness is another type III hypersensitivity response that develops 6 to 14 days after injection with foreign serum (e.g., penicillin, sulfonamides, streptomycin, thiouracils, hydantoin compounds). Deposition of complexes on vessel walls causes complement activation with resultant edema, fever, inflammation of blood vessels and joints, and urticaria.



Clinical Signs and Symptoms


Type III Hypersensitivity





Type IV Hypersensitivity (Cell-Mediated or Delayed)


In cell-mediated hypersensitivity, a reaction occurs 24 to 72 hours after exposure to an allergen.


For example, type IV reactions occur after the intradermal injections of TB antigen. Graft-versus-host disease (GVHD) and transplant rejection are also type IV reactions. In GVHD, immunocompetent donor bone marrow cells (the graft) react against various antigens in the bone marrow recipient (the host), which results in a variety of clinical manifestations, including skin, GI, and hepatic lesions.


Contact dermatitis is another type IV reaction that occurs after sensitization to an allergen, commonly a cosmetic, adhesive, topical medication, drug additive (e.g., lanolin added to lotions, ultrasound gels, or other preparations used in massage or soft tissue mobilization), or plant toxin (e.g., poison ivy).


With the first exposure, no reaction occurs; however, antigens are formed. On subsequent exposures, hypersensitivity reactions are triggered, which leads to itching, erythema, and vesicular lesions. Anyone with known hypersensitivity (identified through the Family/Personal History form) should have a small area of skin tested before use of large amounts of topical agents in the physical therapy clinic. Careful observation throughout the episode of care is required.



Clinical Signs and Symptoms


Type IV Hypersensitivity





Autoimmune Disorders


Autoimmune disorders occur when the immune system fails to distinguish self from nonself and misdirects the immune response against the body’s own tissues. The body begins to manufacture antibodies called autoantibodies directed against the body’s own cellular components or specific organs. The resultant abnormal tissue reaction and tissue damage may cause systemic manifestations varying from minimal localized symptoms to systemic multiorgan involvement with severe impairment of function and life-threatening organ failure.


The exact cause of autoimmune diseases is not understood, but factors implicated in the development of autoimmune immunologic abnormalities may include genetics (familial tendency), sex hormones (women are affected more often than men by autoimmune diseases), viruses, stress, cross-reactive antibodies, altered antigens, or the environment.


Autoimmune disorders may be classified as organ-specific diseases or generalized (systemic) diseases. Organ-specific diseases involve autoimmune reactions limited to one organ. Organ-specific autoimmune diseases include thyroiditis, Addison’s disease, Graves’ disease, chronic active hepatitis, pernicious anemia, ulcerative colitis, and insulin-dependent diabetes. These diseases have been discussed in this text (see the chapter appropriate to the organ involved) and are not covered further in this chapter.


Generalized autoimmune diseases involve reactions in various body organs and tissues (e.g., fibromyalgia, RA, SLE, and scleroderma). Systemic autoimmune diseases lead to a sequence of abnormal tissue reaction and damage to tissue that may result in diffuse systemic manifestations.



Fibromyalgia Syndrome


Fibromyalgia syndrome (FMS) is a noninflammatory condition appearing with generalized musculoskeletal pain in conjunction with tenderness to touch in a large number of specific areas of the body and a wide array of associated symptoms. FMS is much more common in women than in men; it is 2 to 5 times more common than RA. It occurs in age groups from preadolescents to early postmenopausal women.26 The condition is less common in older adults.


There is still much controversy over the exact nature of FMS and even debate over whether fibromyalgia is an organic disease with abnormal biochemical or immunologic pathologic aspects. Some theories suggest that it is a genetically predisposed condition with dysregulation of the neurohormonal and autonomic nervous systems.27 It may be triggered by viral infection, a traumatic event, or stress. The role of inadequate thyroid hormone regulation as a main mechanism of fibromyalgia has been proposed and is under investigation.28


More recent research suggests that chronic pain of this type is centrally mediated since most of these individuals experience pain with input or stimuli that are not usually painful. The problem is with pain or sensory processing, rather than some disease, inflammation, or impairment of the area that actually hurts (e.g., the back, the hips, the wrists).


Functional brain imaging shows areas of the brain that light up when pressure is applied to painful areas of the body. All indications are that once the central pain mechanisms get turned on, they “wind up” until there is pain even when the stimulus (e.g., pressure, heat, cold, electrical impulses) is no longer there. This phenomenon is called sensory augmentation. There is some evidence that people with fibromyalgia have a decrease in their reactivity threshold. In other words, with a low threshold, it only takes a small amount of stimuli before the pain switch gets turned on. Exactly why this happens remains unknown.27


Controversy also existed regarding use of the American College of Rheumatism (ACR) criteria for tender point count in clinical diagnosis of FMS.29 In fact, the original author of the ACR criteria suggested that counting the tender points was “perhaps a mistake” and advised against using it in clinical practice.30 A Symptom Intensity Scale was subsequently developed and validated by Wolfe31,32 to help differentiate FMS from other rheumatologic conditions (e.g., SLE or polymyalgia rheumatica) with similar widespread pain.


Since that time, Wolfe and associates proposed a new set of diagnostic criteria, which the ACR has adopted.33 The new tool focuses on measuring symptom severity rather than relying on the tender point examination. The new criteria use a clinician-queried checklist of painful sites and a symptom severity scale that focuses on fatigue, cognitive dysfunction, and sleep disturbance. Tender point assessment still has value; people with fewer than 11 of the 18 tender points included in the ACR classification criteria may still be diagnosed with fibromyalgia if they have other clinical features consistent with fibromyalgia.34


Fibromyalgia has been differentiated from myofascial pain in that FMS is considered a systemic problem with multiple tender points as one of the key symptoms; there is usually a cluster of associated signs and symptoms. Myofascial pain is a localized condition specific to a muscle (trigger point [TrP]) and may involve as few as one or several areas without associated signs and symptoms.


The hallmark of myofascial pain syndrome is the TrP, as opposed to tender points in FMS. Both disorders cause myalgia with aching pain and tenderness and exhibit similar local histologic changes in the muscle. Painful symptoms in both conditions are increased with activity, although fibromyalgia involves more generalized aching, whereas myofascial pain is more direct and localized (Table 12-2).



There is some clinical evidence that myofascial pain syndrome is linked with the use of hormones containing synthetic progestin (e.g., birth control pills). The effects of progestin on women with fibromyalgia is unknown.35


FMS has striking similarities to chronic fatigue syndrome (CFS), with a mix of overlapping symptoms (about 70%) that have some common biologic denominator. Diagnostic criteria for CFS focus on fatigue, whereas the criteria for FMS focus on pain, the two most prominent symptoms of these syndromes. Studies have shown that CFS and FMS are characterized by greater similarities than differences and both involve the central and peripheral nervous systems as well as the body tissues themselves (Box 12-2).36



BOX 12-2   Fibromyalgia Web Links




• Fibromyalgia Network provides educational materials on fibromyalgia syndrome (FMS) and chronic fatigue syndrome (CFS) and is a very reliable source of information.


    http://www.fmnetnews.com


• American Fibromyalgia Syndrome Association, a nonprofit organization, is dedicated to research, education and patient advocacy for FMS and CFS.


    http://www.afsafund.org


• National Fibromyalgia Association, a nonprofit organization, increases fibromyalgia awareness and improves treatment options.


    http://www.fmaware.org


• Fibromyalgia Research Foundation emphasizes the metabolic basis of fibromyalgia and its treatment.


    http://www.drlowe.com


• Phoenix Publishing, website of physical therapist Janet A. Hulme, MA, PT, includes personal care kits for the management of chronic pain/fibromyalgia. A self-care and treatment manual written by a physical therapist is available to help clients identify which one (or more) subtype they may be and offers specific treatment suggestions based on the subtypes, including modulating the autonomic nervous system through a process called Physiologic Quieting.


    http://www.phoenixpub.com



Risk Factors: Numerous studies have implicated a genetic predisposition related to brain and/or body chemistry, but it has also been shown that a history of childhood trauma, family issues, and/or physical/sexual abuse are significant risk factors.37 Stress, illness, disease, or anything the body perceives as a threat are risk factors for those who develop FMS. But why one person develops this condition, whereas others with equal or worse situations do not, remains a mystery. Anxiety, depression, and posttraumatic stress disorder also seem to be linked with FMS.38 Having a bipolar illness increases the risk of developing FMS dramatically.39



Clinical Signs and Symptoms: The core features of FMS include widespread pain lasting more than 3 months and widespread local tenderness in all clients (Fig. 12-3). Primary musculoskeletal symptoms most frequently reported are (1) aches and pains, (2) stiffness, (3) swelling in soft tissue, (4) tender points, and (5) muscle spasms or nodules. Fatigue, morning stiffness, and sleep disturbance with nonrefreshed awakening may be present but are not necessary for the diagnosis.40



Nontender control points (such as midforehead and anterior thigh) have been included in the examination by some clinicians. These control points may be useful in distinguishing FMS from a conversion reaction, referred to as psychogenic rheumatism, in which tenderness may be present everywhere. However, evidence suggests that individuals with FMS may have a generalized lowered threshold for pain on palpation and the control points may also be tender on occasion. There is also an increased sensitivity to sensory stimulation such as pressure stimuli, heat, noise, odors, and bright lights.41


Symptoms are aggravated by cold, stress, excessive or no exercise, and physical activity (“overdoing it”), including overstretching, and may be improved by warmth or heat, rest, and exercise, including gentle stretching. Smoking has been linked with increased pain intensity and more severe fibromyalgia symptoms, but not necessarily a higher number of tender points. Exposure to tobacco products may be a risk factor for the development of fibromyalgia, but this has not been investigated fully or proven.42


Sleep disturbances in stage 4 of nonrapid eye movement sleep (needed for healing of muscle tissues), sleep apnea, difficulty getting to sleep or staying asleep, nocturnal myoclonus (involuntary arm and leg jerks), and bruxism (teeth grinding) cause clients with FMS to wake up, feeling unrested or unrefreshed, as if they had never gone to sleep (Box 12-3).



BOX 12-3   Fibromyalgia Syndrome (FMS) Screen
























































•Do you have trouble sleeping through the night? YES NO
•Do you feel rested in the morning? YES NO
•Are you stiff and sore in the morning? YES NO
•Do you have daytime fatigue/exhaustion? YES NO
•Can you do the grocery shopping on your own? YES NO
•Can you do your regular daily activities? YES NO
•Do your muscle pain and soreness travel (move around the body)? YES NO
•Do you have tension/migraine headaches? YES NO
•Do you have irritable bowel symptoms (e.g., nausea, diarrhea, stomach cramping)? YES NO
•Do you have swelling, numbness, or tingling in your arms or legs? YES NO
•Are you sensitive to temperature and humidity or changes in the weather? YES NO
•Can you read a book or watch a movie and follow what is happening? YES NO
•Does “brain fog” interfere with your activities or work? YES NO


Key: Researchers have been unable to develop a reliable screening questionnaire for FMS because of the wide-ranging symptoms associated with this condition. This type of screening tool may help the therapist identify potential cases of FMS but should not be relied upon as the only evaluation instrument. See also the Symptom Intensity Scale.31,32



Clinical Signs and Symptoms


Fibromyalgia Syndrome




• Myalgia (generalized aching)


• Fatigue (mental and physical)


• Sleep disturbances, nocturnal myoclonus, nocturnal bruxism


• Restless legs syndrome


• Tender points of palpation


• Chest wall pain mimicking angina pectoris


• Tendinitis, bursitis


• Temperature dysregulation



• Dyspnea, dizziness, syncope


• Headache (throbbing occipital pain)


• Morning stiffness (more than 15 minutes)


• Paresthesia (numbness and tingling)


• Mechanical low back pain with sciatica-like radiation of pain


• Subjective swelling


• Irritable bowel symptoms


• Urinary urgency; irritable bladder syndrome


• Dry eyes/mouth (Sicca syndrome)


• Depression/anxiety


• Cognitive difficulties (e.g., short-term memory loss, decreased attention span; sometimes referred to as fibro fog)


• Premenstrual syndrome (PMS)


• Weight gain from physical inactivity because of pain and fatigue



Differential Diagnosis


Fibromyalgia


Frequently misdiagnosed, fibromyalgia syndrome (FMS) is often confused with any of the following:



Researchers are beginning to identify various subtypes of fibromyalgia and recognize the need for specific intervention based on the underlying subtype. These classifications are based on impairment of the autonomic nervous system. They include the following35,43:



A multidisciplinary or interdisciplinary team approach to this condition requires medical evaluation and treatment as part of the intervention strategy for fibromyalgia. Therapists should refer clients suspected of having fibromyalgia for further medical follow-up.



Rheumatoid Arthritis


Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown cause that can affect various organs but predominantly involves the synovial tissues of the diarthrodial joints. There are more than 100 rheumatic diseases affecting joints, muscles, and extraarticular systems of the body.


Women are affected with RA 2 to 3 times more often than men; however, women who are taking or have taken oral contraceptives are less likely to develop RA. Although it may occur at any age, RA is most common in persons between the ages of 20 and 40 years.



Risk Factors: The etiologic factor or trigger for this process is as yet unknown. Support for a genetic predisposition comes from studies suggesting that RA clusters in families. One gene in particular (HLA-DRB1 on chromosome 6) has been identified in determining susceptibility. RA may be caused by a genetically susceptible person encountering an unidentified agent (e.g., virus, self-antigen), which then results in an immunopathologic response.44 Researchers hypothesize that an infection could trigger an immune reaction that is mediated through multiple complex genetic mechanisms and continues clinically even if the organism is eradicated from the body.


Other nongenetic factors may also contribute to the development of RA. Because arthritis (and many related diseases) is more common in women, hormones have been implicated, but the relationship remains unclear. Environmental and occupational causes, such as chemicals (e.g., hair dyes, industrial pollutants), minerals, mineral oil, organic solvents, silica, toxins, medications, food allergies, cigarette smoking, and stress, remain under investigation as possible triggers for those individuals who are genetically susceptible to RA.45 Many systemic disorders can express themselves through the musculoskeletal system often presenting first with rheumatic manifestations (Box 12-4).46



BOX 12-4


Systemic Conditions Associated with Rheumatic Manifestations






From Andreoli TE, Benjamin I, Griggs RC, et al: Andreoli and Carpenter’s Cecil essentials of medicine, ed 8, Philadelphia, 2010, WB Saunders.



Clinical Signs and Symptoms: Clinical features of RA vary not only from person to person but also in an individual over the disease course. In most people, the symptoms begin gradually during a period of weeks or months. Frequently, malaise and fatigue prevail during this period, sometimes accompanied by diffuse musculoskeletal pain. The multidimensional aspects of rheumatoid arthritic pain can be assessed quantitatively using the Rheumatoid Arthritis Pain Scale (RAPS).47 The complete RAPS is available in the appendix of this article.


Symptoms of an inflammatory arthritis include the spontaneous onset of one or more swollen joints; morning stiffness lasting longer than 45 minutes; and diffuse joint pain and tenderness, particularly involving the metatarsophalangeal (MTP) or metacarpophalangeal (MCP) joints. Inactivity, such as sleep or prolonged sitting, is commonly followed by stiffness. “Morning” stiffness occurs when the person arises in the morning or after prolonged inactivity. The duration of this stiffness is an accepted measure of the severity of the condition.


Clients should be asked: “After you get up in the morning, how long does it take until you are feeling the best you will feel for the day?” Pain and stiffness increase gradually as RA progresses and may limit a person’s ability to walk, climb stairs, open doors, or perform other activities of daily living (ADLs). Weight loss, depression, and low-grade fever can accompany this process.


The inflammatory process may be under way for some time before swelling, tissue reaction, and joint destruction are seen. Structural damage usually begins between the first and second year of the disease. Early medical referral, followed by expedited diagnosis and intervention, results in a much more favorable outcome for persons with RA.


Studies have shown that 70% to 90% of persons with RA have significant joint erosions on x-ray by only 2 years after disease onset and that halting or slowing erosions should be initiated very early on in the course of the disease.48 Having awareness of the group of symptoms that suggest inflammatory arthritis is critical. It is recommended that the criteria for referral of a person with early inflammatory symptoms include significant discomfort on the compression of the metacarpal and metatarsal joints, the presence of three or more swollen joints, and more than 1 hour of morning stiffness.49





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Mar 20, 2017 | Posted by in MANUAL THERAPIST | Comments Off on Screening for Immunologic Disease

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