Serum sickness in humans is a

reaction Reaction may refer to a process or to a response to an action, event, or exposure. Physics and chemistry *Chemical reaction *Nuclear reaction *Reaction (physics), as defined by Newton's third law * Chain reaction (disambiguation) Biology and ...

to proteins in

antiserum In immunology, antiserum is a blood serum containing antibodies (either monoclonal or polyclonal) that is used to spread passive immunity to many diseases via blood donation ( plasmapheresis). For example, convalescent serum, or passive ant ...

derived from a non-human

animal Animals are multicellular, eukaryotic organisms in the Biology, biological Kingdom (biology), kingdom Animalia (). With few exceptions, animals heterotroph, consume organic material, Cellular respiration#Aerobic respiration, breathe oxygen, ...

source, occurring 5–10 days after exposure. Symptoms often include a

rash A rash is a change of the skin that affects its color, appearance, or texture. A rash may be localized in one part of the body, or affect all the skin. Rashes may cause the skin to change color, itch, become warm, bumpy, chapped, dry, cracke ...

joint pain Arthralgia () literally means 'joint pain'. Specifically, arthralgia is a symptom of injury, infection, illness (in particular arthritis), or an allergic reaction to medication Medication (also called medicament, medicine, pharmaceutic ...

fever Fever or pyrexia in humans is a symptom of an anti-infection defense mechanism that appears with Human body temperature, body temperature exceeding the normal range caused by an increase in the body's temperature Human body temperature#Fever, s ...

, and

lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In c ...

. It is a type of

hypersensitivity Hypersensitivity (also called hypersensitivity reaction or intolerance) is an abnormal physiological condition in which there is an undesirable and adverse immune response to an antigen. It is an abnormality in the immune system that causes Imm ...

, specifically immune complex hypersensitivity ( type III). The term

serum sickness–like reaction Serum sickness–like reactions (SSLRs) refer to adverse reactions that have symptoms similar to those of serum sickness (type III immune complex hypersensitivity) but in which immune complexes are not found.James, William; Berger, Timothy; Elston, ...

(SSLR) is occasionally used to refer to similar illnesses that arise from the introduction of certain non-protein substances, such as

penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...

. Serum sickness may be diagnosed based on the symptoms, and using a

blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

and a

urine test A urine test is any medical test performed on a urine specimen. The analysis of urine is a valuable diagnostic tool because its composition reflects the functioning of many body systems, particularly the kidneys and urinary system, and specimens ...

. It may be prevented by not using an antitoxin derived from animal serum, and through prophylactic

antihistamine Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides ...

s or

corticosteroid Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invo ...

s. It usually resolves naturally, but may be treated with corticosteroids, antihistamines, analgesics, and (in severe cases)

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

. It was first characterized in 1906.

Signs and symptoms

Signs and symptoms can take as long as 14 days after exposure to appear. They may include signs and symptoms commonly associated with hypersensitivity or infections. Common symptoms include: *

es and redness. * itching and urticaria. * joint pain ( arthralgia), especially in finger and toe joints. *

, usually appears before rash. This may be as high as 40 °C (104 °F). *

(swelling of

lymph nodes A lymph node, or lymph gland, is a kidney-shaped Organ (anatomy), organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphoc ...

), particularly near the site of injection. *

malaise In medicine, malaise is a feeling of general discomfort, uneasiness or lack of wellbeing and often the first sign of an infection or other disease. It is considered a vague termdescribing the state of simply not feeling well. The word has exist ...

. Other symptoms include glomerulonephritis, blood in the urine,

splenomegaly Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulat ...

(enlarged

spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...

hypotension Hypotension, also known as low blood pressure, is a cardiovascular condition characterized by abnormally reduced blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood and is ...

(decreased

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

), and in serious cases circulatory shock.

Complications

Rarely, serum sickness can have severe complications. These include neuritis,

myocarditis Myocarditis is inflammation of the cardiac muscle. Myocarditis can progress to inflammatory cardiomyopathy when there is associated ventricular remodeling and cardiac dysfunction due to chronic inflammation. Symptoms can include shortness of bre ...

, laryngeal oedema,

pleurisy Pleurisy, also known as pleuritis, is inflammation of the membranes that surround the lungs and line the chest cavity (Pulmonary pleurae, pleurae). This can result in a sharp chest pain while breathing. Occasionally the pain may be a constant d ...

, and

Guillain–Barré syndrome Guillain–Barré syndrome (GBS) is a rapid-onset Paralysis, muscle weakness caused by the immune system damaging the peripheral nervous system. Typically, both sides of the body are involved, and the initial symptoms are changes in sensation ...

Causes

Serum sickness is a

type III hypersensitivity Type III hypersensitivity, in the Gell and Coombs classification of allergic reactions, occurs when there is accumulation of immune complexes (antigen-antibody complexes) that have not been adequately cleared by innate immune cells, giving ris ...

reaction, caused by immune complexes. When an

is given, the human

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

can mistake the

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s present for harmful

antigen In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s. The body produces antibodies, which combine with these proteins to form immune complexes. These complexes precipitate, enter the walls of blood vessels, and activate the complement cascade, initiating an inflammatory response and consuming much of the available

complement component 3 Complement may refer to: The arts * Complement (music), an interval that, when added to another, spans an octave ** Aggregate complementation, the separation of pitch-class collections into complementary sets * Complementary color, in the vi ...

(C3). They can be found circulating in the blood, which differentiates serum sickness from serum sickness-like reaction. The result is a leukocytoclastic

vasculitis Vasculitis is a group of disorders that destroy blood vessels by inflammation. Both artery, arteries and veins are affected. Lymphangitis (inflammation of lymphatic vessels) is sometimes considered a type of vasculitis. Vasculitis is primarily c ...

. This results in hypocomplementemia, a low C3 level in serum. They can also cause more reactions, causing the typical symptoms of serum sickness. This is similar to a generalised Arthus reaction.

Antitoxins and antisera

Serum sickness is usually a result of exposure to

antibodies An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as bacteria and viruses, including those that caus ...

derived from animals. These sera or

antitoxin An antitoxin is an antibody with the ability to neutralize a specific toxin. Antitoxins are produced by certain animals, plants, and bacterium, bacteria in response to toxin exposure. Although they are most effective in neutralizing toxins, the ...

s are generally given to prevent or treat an

infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmis ...

or envenomation (venomous bite).

Drugs

Serum sickness may be caused by some routine

medications Medication (also called medicament, medicine, pharmaceutical drug, medicinal product, medicinal drug or simply drug) is a drug used to medical diagnosis, diagnose, cure, treat, or preventive medicine, prevent disease. Drug therapy (pharmaco ...

. Some of the drugs associated with serum sickness are: *

allopurinol Allopurinol is a medication used to decrease hyperuricemia, high blood uric acid levels. It is specifically used to prevent gout, prevent specific types of kidney stones and for the high uric acid levels that can occur with chemotherapy. It i ...

* barbiturates *

captopril Captopril, sold under the brand name Capoten among others, is an ACE inhibitor, angiotensin-converting enzyme (ACE) inhibitor used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first oral ACE inh ...

cephalosporins The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''. Together with cephamycins, they constitute a subgroup of β-lactam antibiotic ...

* crofab * griseofulvin *

penicillins Penicillins (P, PCN or PEN) are a group of β-lactam antibiotics originally obtained from ''Penicillium'' moulds, principally '' P. chrysogenum'' and '' P. rubens''. Most penicillins in clinical use are synthesised by '' P. chrysogenum'' ...

* phenytoin * procainamide *

quinidine Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is a diastereomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...

streptokinase Streptokinase is a thrombolysis, thrombolytic medication activating plasminogen by nonenzymatic mechanism. As a medication it is used to thrombolysis, break down clots in some cases of myocardial infarction (heart attack), pulmonary embolism, an ...

sulfonamides In organic chemistry, the sulfonamide functional group (also spelled sulphonamide) is an organosulfur group with the Chemical structure, structure . It consists of a sulfonyl group () connected to an amine group (). Relatively speaking this gro ...

rituximab Rituximab, sold under the brand name Rituxan among others, is a monoclonal antibody medication used to treat certain autoimmune diseases and types of cancer. It is used for non-Hodgkin lymphoma, chronic lymphocytic leukemia (in children and ad ...

ibuprofen Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes dysmenorrhea, painful menstrual periods, migraines, and rheumatoid arthritis. It can be taken oral administration, ...

infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases. This includes Crohn's disease, ulcerative colitis, rheumatoid arthritis, ankylosing ...

oxycodone Oxycodone, sold under the brand name Roxicodone and OxyContin (which is the extended-release form) among others, is a semi-synthetic opioid used medically for the treatment of moderate to severe pain. It is highly addictive and is a commonly ...

Others

Allergenic extracts,

hormones A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

and

vaccines A vaccine is a biological preparation that provides active acquired immunity to a particular infectious or malignant disease. The safety and effectiveness of vaccines has been widely studied and verified. A vaccine typically contains an ag ...

can also cause serum sickness. However, according to the Johns Hopkins Bloomberg School of Public Health, routinely recommended vaccinations to the general population in the U.S have not been shown to cause serum sickness, as of 2012.

Diagnosis

Diagnosis is based on history given by patient, including recent medications. A blood sample may be taken and tested, which will show

thrombocytopenia In hematology, thrombocytopenia is a condition characterized by abnormally low levels of platelets (also known as thrombocytes) in the blood. Low levels of platelets in turn may lead to prolonged or excessive bleeding. It is the most common coag ...

(low

platelets Platelets or thrombocytes () are a part of blood whose function (along with the coagulation factors) is to react to bleeding from blood vessel injury by clumping to form a blood clot. Platelets have no cell nucleus; they are fragments of cyto ...

leukopenia Leukopenia () is a decrease in the number of white blood cells (leukocytes). It places individuals at increased risk of infection as white blood cells are the body's primary defense against infections. Signs and symptoms Symptoms may include: * s ...

(low

white blood cells White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

), high sedimentation of

red blood cells Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

, and a decrease in the complement proteins C3 and C4. A urine sample may be taken and tested, which will show

proteinuria Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become fo ...

, and sometimes

hematuria Hematuria or haematuria is defined as the presence of blood or red blood cells in the urine. "Gross hematuria" occurs when urine appears red, brown, or tea-colored due to the presence of blood. Hematuria may also be subtle and only detectable with ...

(blood in the urine, with hemoglobinuria).

Differential diagnosis

Similar skin symptoms may be caused by lupus, erythema multiforme, and

hives Hives, also known as urticaria, is a kind of skin rash with red or flesh-colored, raised, itchy bumps. Hives may burn or sting. The patches of rash may appear on different body parts, with variable duration from minutes to days, and typically ...

Prevention

Avoidance of antitoxins that may cause serum sickness is the best way to prevent serum sickness. Sometimes, the benefits of using an antitoxin outweigh the risks in the case of a life-threatening

bite Biting is an action involving a set of teeth closing down on an object. It is a common zoological behavior, being found in toothed animals such as mammals, reptiles, amphibians, fishes, and arthropods. Biting is also an action humans participate ...

or sting. Prophylactic

s or

s may be used with an antitoxin. Skin testing may be used beforehand in order to identify individuals who may be at risk of a reaction.

Physician A physician, medical practitioner (British English), medical doctor, or simply doctor is a health professional who practices medicine, which is concerned with promoting, maintaining or restoring health through the Medical education, study, Med ...

s should make their patients aware of the drugs or antitoxins to which they are allergic if there is a reaction. The physician will then choose an alternate antitoxin if it is appropriate, or continue with prophylactic measures. This is important if a patient has received an antitoxin before, as the serum sickness caused can be worse and occur more quickly.

Treatment

Antiserum In immunology, antiserum is a blood serum containing antibodies (either monoclonal or polyclonal) that is used to spread passive immunity to many diseases via blood donation ( plasmapheresis). For example, convalescent serum, or passive ant ...

or drug treatment should be stopped as soon as possible. Once treatment has stopped, symptoms usually resolve within seven days. Outcomes are generally good.

Corticosteroids Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are invol ...

antihistamines Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides r ...

, and analgesics are the main line of treatment. The choice depends on the severity of the reaction.

Prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

may be used in severe cases. Use of plasmapheresis has also been described.

Epidemiology

Serum sickness is becoming less common over time. Many drugs based on animal serum have been replaced with artificial drugs.

History

Serum sickness was first characterized by

Clemens von Pirquet Clemens Peter Freiherr von Pirquet (12 May 187428 February 1929) was an Austrian scientist and pediatrician best known for his contributions to the fields of bacteriology and immunology. Career Born in Vienna, he studied theology at the Universit ...

and Béla Schick in 1906.

References

External links

Serum sickness-like reactions
{{DEFAULTSORT:Serum Sickness Complications of surgical and medical care