When first exposed to drugs containing proteins of other species, individuals showcase the signs and symptoms after about 7 – 10 days. When exposed for the second time, the symptoms appear pretty fast within 1 – 4 days [9]. The signs and symptoms of serum sickness include the following:

• Fever accompanied by body ache
• Malaise
• Fatigue
• Development of rashes, hives
• Joint pain
• Abdominal pain accompanied by diarrhea
• Wheezing
• Itching
• Flushing
• Inflammation of the lymph nodes

• Generalized Lymphadenopathy

  Manifestations often include fever, rash, and joint inflammation, but generally lack generalized lymphadenopathy and evidence of systemic vasculitis such as glomerulonephritis [ 8 ]. [biomedcentral.com]

• Fever

  Due to the patient's fever, myalgias, mild transaminitis, diffuse erythematous rash, and depressed total serum complement, it was determined that the patient had serum sickness secondary to treatment with rivaroxaban. [ncbi.nlm.nih.gov]

  He was reevaluated two weeks after this treatment and was found to have no further evidence of fevers, rash, or joint involvement. [biomedcentral.com]

• Malaise

  Symptoms included disabling joint pain, proteinuria, fever, rash, and malaise. To our knowledge, this adverse drug reaction has not been described in association with 6-mercaptopurine. [ncbi.nlm.nih.gov]

  Affected individuals complain of skin rashes that develop at the site of injection, fever accompanied by feeling of malaise and body ache. [symptoma.com]

• Fatigue

  The signs and symptoms of serum sickness include the following: Fever accompanied by body ache Malaise Fatigue Development of rashes, hives Joint pain Abdominal pain accompanied by diarrhea Wheezing Itching Flushing Inflammation of the lymph nodes At [symptoma.com]

  Provide periods of rest to promote sleep and decrease fatigue. Organize patient care and activities to provide uninterrupted rest. Perform hand hygiene. Maintain adequate nutrition and adequate rest. Provide a safe environment. [quizlet.com]

  I am stuck indoors now, as being out in the sun brings on a rash on my body, followed by a flu like feeling, fatigue and more joint pain. Hoping this goes away once my body gets rid of the medicine. [kickas.org]

• Dyspnea

  Symptoms include fever, arthralgias, myalgias, skin eruptions, lymphadenopathy, chest pain, and dyspnea. [sideeffects.embl.de]

  However, dyspnea and cyanosis are not uncommon. [whale.to]

  Most hypersensitivity reactions, which include urticaria, dyspnea, and/or hypotension, have occurred during or within 2 hours of REMICADE infusion. [kickas.org]

• Cough

  A 19-year-old female presented with gross swelling of the face, significant aggravation of her existing acne, a mild cough and a little difficulty in breathing since 2 days. [ijdvl.com]

• Nausea

  On admission to the Emergency Department, physical examination included the following vital signs and findings: pulse 76 beats/min, blood pressure 90/60 mm Hg, nausea, vomiting, foot and distal leg swelling, and normal fetal monitoring. [ncbi.nlm.nih.gov]

  Symptoms include skin eruption, itching, swelling of the face and extremities, fever, joint pain and sometimes swelling, abdominal pain, nausea, and vomiting; severe cases may also show neurological symptoms. [britannica.com]

  Swelling, especially around the face and neck, facial flushing, muscle pain, lymph node swelling, joint pain, or arthritis involving multiple joints (ankle, knee, wrist, fingers, toes), and complaints of abdominal cramping, diarrhea, and nausea also occur [drhull.com]

• Diarrhea

  After taking this treatment for 1 month, she presented with fever, diarrhea, localized edemas, generalized pruritic papular and erythematous rash and lymphadenopathies. She presented the same symptoms after oral intake of metamizole. [ncbi.nlm.nih.gov]

  Individuals also experience diarrhea, abdominal pain, flushing, wheezing, itching and inflammation of lymph nodes. [symptoma.com]

  Mom denies history of vomiting or diarrhea. there are no respiratory symptoms. She has no involvement of her eyes or mouth. [pemcincinnati.com]

  Swelling, especially around the face and neck, facial flushing, muscle pain, lymph node swelling, joint pain, or arthritis involving multiple joints (ankle, knee, wrist, fingers, toes), and complaints of abdominal cramping, diarrhea, and nausea also occur [drhull.com]

• Vomiting

  A 40 y/o woman with relapsing multiple sclerosis presented with vomiting, fever, diffuse rash, joint and lumbar back pain, distal lower limb parasthesia. [n.neurology.org]

  On admission to the Emergency Department, physical examination included the following vital signs and findings: pulse 76 beats/min, blood pressure 90/60 mm Hg, nausea, vomiting, foot and distal leg swelling, and normal fetal monitoring. [ncbi.nlm.nih.gov]

  Mom denies history of vomiting or diarrhea. there are no respiratory symptoms. She has no involvement of her eyes or mouth. [pemcincinnati.com]

  Symptoms include skin eruption, itching, swelling of the face and extremities, fever, joint pain and sometimes swelling, abdominal pain, nausea, and vomiting; severe cases may also show neurological symptoms. [britannica.com]

• Abdominal Pain

  Individuals also experience diarrhea, abdominal pain, flushing, wheezing, itching and inflammation of lymph nodes. [symptoma.com]

  Symptoms include skin eruption, itching, swelling of the face and extremities, fever, joint pain and sometimes swelling, abdominal pain, nausea, and vomiting; severe cases may also show neurological symptoms. [britannica.com]

  Less common features are: Headache Muscle pain Nausea, vomiting, diarrhoea, abdominal pain Enlarged lymph glands Other skin rashes such as morbilliform, scarlatiniform or erythema multiforme -like. [dermnetnz.org]

• Abdominal Cramps

  Swelling, especially around the face and neck, facial flushing, muscle pain, lymph node swelling, joint pain, or arthritis involving multiple joints (ankle, knee, wrist, fingers, toes), and complaints of abdominal cramping, diarrhea, and nausea also occur [drhull.com]

  cramping Causes Serum sickness occurs following injection with antiserum. [mddk.com]

  Other signs and symptoms include: Skin rash, hives Joint pain Fever Malaise (feeling unwell) Swollen lymph nodes Itching Wheezing Flushing Diarrhea, nausea, and abdominal cramping Antigens, proteins the body mistakenly identifies as harmful, cause your [pennstatehershey.adam.com]

• Arthralgia

  We describe the case of a 3-year-old girl with urticaria, fever, and arthralgia that appeared 8 days after starting cefaclor therapy for otitis media. [ncbi.nlm.nih.gov]

• Arthritis

  We report a patient who developed a serum sickness-like illness characterized by fever, arthritis, haematuria and a purpuric eruption 7 days following streptokinase therapy for myocardial infarction. [ncbi.nlm.nih.gov]

  Definition of serum sickness : an allergic reaction to the injection of foreign serum manifested by hives, swelling, eruption, arthritis, and fever First Known Use of serum sickness circa 1913, in the meaning defined above Learn More about serum sickness [merriam-webster.com]

• Myalgia

  Patient was placed on iv methylprednisolone therapy, and within 18 h a significant improvement was noted in her myalgias and rash. [ncbi.nlm.nih.gov]

• Joint Swelling

  A 37-year-old woman with plaque psoriasis who had been treated with efalizumab for 2 months developed a fever, erythematous rash, and progressive joint swelling and pain that required hospitalization. [ncbi.nlm.nih.gov]

  Symptoms include flu-like symptoms of fever, itchy hive like and bruising rashes, swelling of the lymph glands or joint swelling and pain can result. Symptoms generally resolve over a period of days or weeks. [allergycapital.com.au]

  Last year, he developed a reaction to Augmentin (amoxicillin clavulanate) with fever, joint swelling and hives. He had been on Augmentin previously without clinical symptoms. This year, he needed another course of antibiotics. [allergycases.blogspot.com]

  Pain in joints, mostly large joint are first affected. After few days, patient may also experience pain in smaller joints. Swelling of regional lymph nodes. Swelling of legs, face and arms. [tandurust.com]

  They checked her over once again and found all her lymph nodes were inflammed her liver and spleen were very enlarged, she was dehydrated, the pain was in her joints and she had joint swelling, her belly was so inflammed she looked like one of those pregnant [ourhealth.com]

• Symmetrical Arthritis

  arthritis, especially knees and small joints of the hands and foot Lymphadenopathy Rare complications: Neurological impairments Glomerulonephritis Pathophysiology: The true mechanism of non-protein drug induced SSLR is not known but in the case of Cefaclor [scepticemia.com]

• Urticaria

  […] serum sickness when they act as haptens inducing antibody responses 999.5 Excludes Applies To Intoxication by serum Protein sickness Serum rash Serum sickness Urticaria due to serum [icd9data.com]

  We describe the case of a 7-year-old boy with urticaria, fever, and arthritis that appeared 10 days after starting cefditoren therapy for acute tonsillopharyngitis, which was diagnosed as a serum sickness-like reaction due to this medication. [ncbi.nlm.nih.gov]

  On DermNet NZ Serum sickness Drug eruptions Urticaria Other websites Medscape Reference: Serum Sickness Serum Sickness Serum Sickness Books about skin diseases See the DermNet NZ bookstore . [dermnetnz.org]

• Eruptions

  We report a patient who developed a serum sickness-like illness characterized by fever, arthritis, haematuria and a purpuric eruption 7 days following streptokinase therapy for myocardial infarction. [ncbi.nlm.nih.gov]

  Definition of serum sickness : an allergic reaction to the injection of foreign serum manifested by hives, swelling, eruption, arthritis, and fever First Known Use of serum sickness circa 1913, in the meaning defined above Learn More about serum sickness [merriam-webster.com]

  Simultaneously, a cutaneous eruption appeared which was initially limited to bilateral upper extremities but soon involved his trunk, back, face and lower extremities. [biomedcentral.com]

• Skin Rash

  A 59-year-old male suffered from fever, headaches, polyarthritis, and diffused skin rash approximately 10 days after administration of the antivenin. [ncbi.nlm.nih.gov]

  It is characterized by the triad of fever, joint pain or swelling and skin rash. Serum sickness is a self-limiting condition that normally resolves within several days. [mddk.com]

• Angioedema

  We describe two additional cases of serum sickness reactions due to minocycline, characterized by erythematous rash, arthropathy, and in one case, angioedema. [ncbi.nlm.nih.gov]

  […] marginatum / rheumatic fever Eosinophilic cellulitis Neonatal lupus erythematosus Drug hypersensitivity syndrome (drug rash with eosinophilia and systemic symptoms [DRESS]) Serum sickness Leukocytoclastic vasculitis Exanthematous drug eruption Hereditary angioedema [visualdx.com]

  Complications include: Inflammation of the blood vessels Swelling of the face, arms, and legs ( angioedema ) Call your provider if you received medicine or antiserum in the last 4 weeks and have symptoms of serum sickness. [medlineplus.gov]

• Flushing

  Individuals also experience diarrhea, abdominal pain, flushing, wheezing, itching and inflammation of lymph nodes. [symptoma.com]

  Swelling, especially around the face and neck, facial flushing, muscle pain, lymph node swelling, joint pain, or arthritis involving multiple joints (ankle, knee, wrist, fingers, toes), and complaints of abdominal cramping, diarrhea, and nausea also occur [drhull.com]

  Flushed face. Wheezing sound in chest and discomfort while breathing. How Long Does Serum Sickness Last & How To Treat It? Serum sickness develops after delayed period of time. It may take 7 to 10 days for the appearance of symptoms. [tandurust.com]

  Other signs and symptoms include: Skin rash, hives Joint pain Fever Malaise (feeling unwell) Swollen lymph nodes Itching Wheezing Flushing Diarrhea, nausea, and abdominal cramping Antigens, proteins the body mistakenly identifies as harmful, cause your [pennstatehershey.adam.com]

• Facial Swelling

  The typical triad of serum sickness comprises fever, rash and joint pain/swelling (arthritis or arthralgia ). There is also often facial swelling and lymph node enlargement. The kidneys are commonly affected. [dermnetnz.org]

  Serum sickness is characterized by the triad of: Onset of fever Development of skin rash similar to urticaria Joint pain and swelling Other symptoms may include the following: Facial swelling Enlargement of the lymph nodes Itching Malaise Wheezing Blurry [mddk.com]

• Facial Edema

  He presented with renal failure and several of the classic signs reported in early descriptions of serum sickness by Clemens von Pirquet and Bela Schick including lymphadenopathy, urticarial skin eruption and facial edema. [ncbi.nlm.nih.gov]

  It is notable that none of the 14 HCP who had a serum sickness-like reaction reported having red eyes, facial edema associated with oculorespiratory syndrome, or any respiratory symptoms after receipt of the GPO-MBP vaccine [ 11, 12 ]. [academic.oup.com]

  Symptoms associated with these reactions include fever, rash, headache, sore throat, myalgias, polyarthralgias, hand and facial edema and/or dysphagia. [kickas.org]

• Rabies

  Serum sickness is a side effect that can occur after you take medication for an immune system condition, or after you've been given an antiserum (a treatment that protects against certain germs or poisons, such as snake venom or rabies). [sharecare.com]

  In the US, about 2-5% and 16% of tetanus antitoxin and rabies antitoxin users, respectively, were afflicted with the sickness. [medicalterms.info]

  Products derived from human serum have replaced the most frequently used antitoxins, which are rabies and tetanus horse serum antitoxins. [whale.to]

  (antibodies form against side chains) Minocycline TMP/SMX Rifampin Penicillins Streptokinase Meropenem Monoclonal antibodies, especially rituximab SSRIs Bupropion Propranolol Vaccines, has been reported after H1N1 vaccine Equine diphtheria antiserum Rabies [unboundmedicine.com]

  Antiserum injections are also given to patients who are exposed to tetanus and rabies germs. In serum sickness, the immune system of the body mistakenly recognizes proteins present in antiserum as harmful substances. [tandurust.com]

• Peripheral Neuropathy

  The clinical presentation of serum sickness is described as symptoms including fever, rash, arthralgia, nausea, vomiting, headaches and neurologic manifestations which can include peripheral neuropathy or brachial neuritis. [n.neurology.org]

  Neurologic manifestations include peripheral neuropathy, brachial plexus neuritis, optic neuritis, cranial nerve palsies, Guillain-Barré syndrome, and encephalomyelitis. Pulmonary manifestations, such as pleurisy, are rare. [whale.to]

• Guillain-Barré Syndrome

  Neurologic manifestations include peripheral neuropathy, brachial plexus neuritis, optic neuritis, cranial nerve palsies, Guillain-Barré syndrome, and encephalomyelitis. Pulmonary manifestations, such as pleurisy, are rare. [whale.to]

At the preliminary level, a complete medical history including drugs taken by the individual is gathered. This baseline information provides an idea about serum sickness. To further confirm the condition, urine test is done which would reveal presence of blood and proteins. In addition, blood test would indicate development of inflammation of the blood vessels or presence of immune complexes.

• Hospitalization is usually not required for patients with serum sickness. Symptoms begin to improve within 48 – 72 hours after initiation of treatment.
• In order to correct serum sickness, the medication that caused such a condition to develop is stopped. Thereafter, if there is presence of rashes on the body then corticosteroid creams and ointments are administered for application over the affected area. To decrease the illness duration and relieve the itching and discomfort due to the rashes, antihistamines are given.
• NSAIDs are given to relieve joint pain. However, individuals with a history ofrenal disorders should be given this medication with caution. Other substitutes should be considered for such patients. Severe cases of serum sickness may warrant a brief course of corticosteroids and plasmapharesis to relieve its symptoms [10].

The prognosis of the condition is usually favorable and with prompt treatment symptoms generally resolve within few days.

Complications

Complications result when individuals are exposed to the same drugs or antiserum that had caused serum sickness in the past. The possible complications of serum sickness include the following:

• Angioedema characterized by inflammation of the arms, face and legs
• Inflammation of the blood vessels
• Anaphylactic shock

Reaction to certain class of drugs containing proteins is the major cause of serum sickness. Amongst all drugs, penicillin is known to be the most common causative factor. The following types of drugs that contain protein components derived from other species are known to play a role in causation of the disease:

• Vaccines
• Antitoxins [2]
• Streptokinase [3]
• Monoclonal antibodies
• Polyclonal antibodies
• Diuretics known as thiazides
• Fluoxetine
• Barbiturates
• Bupropion [4]

In addition to the above mentioned drugs, snake venom antiserum also triggers the development of serum sickness.

In the condition of serum sickness, the immune system of the body behaves in a different manner and falsely regards the protein in the antiserum as invaders (especially from animal sources) and attacks it [5]. Such an event gives rise to various symptoms. Insect stings from bees and mosquitoes have been casually documented to cause serum sickness among afflicted individuals [6].

The incidence of serum sickness has undergone a steady decline because of the modern refining processes in the preparation of antiserum and drugs [7]. In addition, it also gets worth mentioning that the dosage is also important for triggering serum sickness. It has been estimated that 10% of individuals who were administered 10 mL of tetanus antitoxin exhibited symptoms of serum sickness. On the other hand, almost all patients developed the condition when given higher doses of more than 80 mL antitoxin.

In the condition of serum sickness, the immune system of the body regards the proteins present in the antiserum as invaders and attacks them. As a result, the body produces antibodies which in turn combine with the protein to form immune complexes. These immune complexes enter the blood vessels and generate several inflammatory responses that give rises to an array of associated conditions [8].

So far no guidelines have been provided to prevent the onset of serum sickness. However, the recurrence of the condition can be prevented by avoiding those medications that had caused serum sickness in the past. Individuals should inform the health care provider if they are sensitive to antiserum. In such cases, the individual is temporarily desensitized for that particular antiserum. Before administration of the antiserum, a skin test should be conducted to check for sensitivity towards the serum.

Serum sickness is a type of allergic reaction experienced by individuals in response to certain medications containing proteins or antiserum given to combat specific disease conditions. It is considered as a type III hypersensitivity reaction exhibited when the body is given drugs containing protein [1].

The onset of the condition is delayed by 7 – 10 days after the initial exposure. However, if the individual is again exposed to the allergic components then the symptoms begin to show effect within 1 – 4 days. The condition was first described in the year 1906 by Clemens Von Pirquet and Bela Schick.

Definition

Serum sickness is a condition characterized by abnormal behavior of the immune system in response to certain drugs containing protein of other species or antiserum. Antiserum is the liquid part of the blood containing antibodies that is administered to individuals for protection against effects of poison or germs. Serum sickness is also known as type III hypersensitivity reaction.

Cause

Penicillin is the most common cause of serum sickness. In addition, drugs prescribed for treating depression, products that contain aspirin, diuretics such as thiazides and other medications are also known to cause serum sickness. Individuals who are given antiserum after snake bite or an attack of rabies also exhibit symptoms of allergic reaction.

Symptoms

Symptoms of serum sickness usually develop after 7 – 10 days of initial exposure. Affected individuals complain of skin rashes that develop at the site of injection, fever accompanied by feeling of malaise and body ache. Individuals also experience diarrhea, abdominal pain, flushing, wheezing, itching and inflammation of lymph nodes.

Diagnosis

Diagnosis of serum sickness begins with a past medical history which would also contain information about the drugs taken by the individual. To further confirm the diagnosis, blood and urine tests are also carried out. If urine tests reveal presence of blood and proteins, and blood tests shows immune complexes, then the diagnosis of serum sickness is confirmed.

Treatment

The medications that caused serum sickness are immediately stopped. Thereafter, corticosteroid creams are given for relieving the rash and NSAIDs are administered for relieving joint pain. Individuals with kidney disorders should be given NSAIDs with caution. In addition to these, nutritional supplements may also be given as supportive therapy to strengthen the immune system.

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2. Mannik M. Serum Sickness and Pathophyisology of immune complexes. Clin Immunology Principles and Practice. St Louis, Mo: Mosby 1996:1062-71.
3. Frank MM, Lawley TJ. Immune complexes and allergic disease. In: Middleton E Jr, ed. Allergy Principles and Practice. 5th ed. St Louis, Mo: Mosby; 1998:704-6.
4. Wooltorton E. Bupropion (Zyban, Wellbutrin SR): reports of deaths, seizures, serum sickness. CMAJ. Jan 8 2002; 166(1):68.
5. Lawley TJ, Bielory L, Gascon P, Yancey KB, Young NS, Frank MM. A prospective clinical and immunologic analysis of patients with serum sickness. N Engl J Med. Nov 29 1984; 311(22):1407-13.
6. Lazoglu AH, Boglioli LR, Taff ML, Rosenbluth M, Macris NT. Serum sickness reaction following multiple insect stings. Ann Allergy Asthma Immunol. Dec 1995; 75(6 Pt 1):522-4.
7. Dixon FJ, Cochrane CC. Immune complex injury. In: Samter M, ed. Immunological Diseases. 4th Ed. New York, NY: Little, Brown and Company; 1988:233.
8. Sicherer SH, Leung DYM. Serum sickness. In: Kliegman, ed. Nelson Textbook of Pediatrics. 18th ed. Online Edition, Chapter 149.
9. Lawley TJ, Frank MM. Immune complexes and allergic diseases. In: Middleton E Jr, ed. Allergy Principles and Practice. 4th ed. St. Louis, Mo: Mosby; 1993:990.
10. Erffmeyer JE. Serum sickness. Ann Allergy. Feb 1986; 56(2):105-9.