Viral Arthritis

Viruses can cause infection or act as cofactors in the development of rheumatic diseases. Viral infection depends on both host and viral factors. Key host factors include age, sex, genetic background, infection history, and immune response. Key viral factors include mode of host entry, tissue tropism, replication, effects of cytokines, ability to establish persistent or latent viral infections, and alterations of host antigens. Infected cells can undergo apoptosis (programmed cell death).

The immune complexes from an antibody response can be deposited at sites of viral infection or in the synovium. Virus-induced autoimmunity, polyclonal B-cell activation, and immunodeficiency may result in opportunistic infection, largely because of an inability of the immune system to eliminate the virus (eg, HIV, human T-lymphotropic virus [HTLV]-1, or hepatitis C virus [HCV]). Molecular mimicry may cause abnormal self-reactivity by altering immune tolerance.[2]

Viruses that can give rise to viral arthritis include the following[3] :

• Parvovirus B19
• Hepatitis viruses ( hepatitis A virus [HAV], hepatitis B virus [HBV], and HCV)
• Rubella virus
• Alphaviruses and flaviviruses
• Retroviruses

Parvovirus B19

Parvovirus B19 is a small, single-stranded DNA virus that replicates in dividing cells and thus has a remarkable tropism for human erythroid progenitor cells. It may be responsible for about 12% of cases of sudden-onset polyarticular arthritis, especially in adults frequently exposed to children (eg, schoolteachers and pediatric nurses, who have a 50% risk of infection). Outbreaks of erythema infectiosum commonly occur in late winter and spring, but the condition can be observed during summer and fall, with sporadic cases occurring throughout the year.

Respiratory secretions are a vector for transmission. The use of blood products, especially clotting factor concentrates, is another mode of transmission.[4] Vertical transmission may occur from mother to fetus. The highest morbidity to the fetus is during the first or second trimester.

Hepatitis viruses

HAV infection accounts for 10-14% of cases of viral arthritis. Arthralgia and skin rash occur during the acute phase. Transmission is via the fecal-oral route.

HBV is an enveloped, double-stranded DNA virus. HBV infection causes 20-25% of cases of viral arthritis. Transmission can be parenteral or sexual.

HCV is an enveloped, single-stranded RNA virus. HCV infection occurs worldwide. Transmission can be parenteral or, uncommonly, sexual.

Rubella virus

Rubella virus is the sole member of the Rubivirus genus (Togaviridae family) and is a single-stranded RNA virus. Rubella virus naturally infects humans, primarily women, and is transmitted via nasopharyngeal secretions, with a peak incidence in late winter and spring. Approximately 50-75% of rubella virus infections are symptomatic; the rest are subclinical.

Alphaviruses

Alphaviruses constitute a genus of the Togaviridae family. Approximately five to six types of alphavirus infection cause rheumatic symptoms and fever as major features; all are mosquito-borne. Geographic distributions are as follows:

• Chikungunya virus – Historically,, East Africa, India, Southeast Asia, and Philippines[5] ; however, in 2013 the virus spread to the Caribbean and in 2014 it reached the United States[6]  

• O’nyong-nyong virus – East Africa

• Ross River virus – Australia, New Zealand, and South Pacific islands

• Mayaro virus – South America

• Sindbis virus – Europe, Asia, Africa, Australia, and Philippines

• Barmah Forest virus – Australia

Chen and colleagues found that alphavirus infection results in bone loss in a mouse model of Ross River virus, and that bone loss was prevented by inhibition of interleukin-6 (IL-6). Alphaviruses may disrupt bone homeostasis, and osteoblasts may contribute to alphavirus-induced arthritis by regulating IL-6 and contribute to bone loss by disrupting the receptor activator of nuclear factor-kappaB ligand/osteoprotegerin balance.[7]

Retroviruses

HIV infection is associated with several rheumatic manifestations, of which arthralgia is the most common (25-40% of cases).[8] Other manifestations include the following:

• Psoriatic arthritis
• Rheumatoid arthritis
• Painful articular syndrome (10%)
• Undifferentiated spondyloarthropathy
• Inflammatory myopathy
• Systemic vasculitis
• Diffuse infiltrative lymphocytosis syndrome (5%)
• Fibromyalgia (30%)
• Avascular necrosis
• Gout

Arthritis (ie, arthralgia and arthritic syndromes) in association with HIV infection has been reported in the United States, Europe, and Africa. It can occur at any stage of HIV infection. The pattern of HIV-associated arthritis is similar to that of arthritis associated with other viral disorders: acute onset, short duration, recurrences, and no erosive changes. Patients infected with HIV are not at increased risk for the development of septic arthritis but they do have an increased frequency of pyomyositis.

Diffuse infiltrative lymphocytosis syndrome (DILS) resembles Sjögren syndrome, with sicca symptoms, salivary gland enlargement, and lymphocytic infiltration involving the lungs, gastrointestinal (GI) tract, and kidneys. To make the diagnosis, there needs to be histological confirmation of salivary or lacrimal lymphocytic infiltration, with granulomatous or neoplastic etiologies excluded. In contrast to Sjögren syndrome, the lymphocytes infiltrating these sites in diffuse infiltrative lymphocytosis syndrome are predominantly CD8+ (rather than CD4+) T cells and the presence of elevated titers of circulating and infiltrating CD8+ lymphocytes is a key feature of the pathophysiology.[9]

Reactive arthritis in association with HIV infection occurs in 0.5-3% of cases. Oligoarthritis of the lower extremities and urethritis is common, but conjunctivitis is rare. Severe erosive arthritis is possible and can be very debilitating.  Human leukocyte antigen (HLA)–B27 is found in 80–90 % of Caucasians with HIV-associated reactive arthritis, while studies of Africans with HIV-associated reactive arthritis have found nearly all to be HLA-B27-negative. As in HIV-uninfected patients, antecedent history of genitourinary and gastrointestinal infection is common. This point could hold the key to explaining the geographical differences observed in the prevalence of reactive arthritis – countries with higher rates of HIV contracted through intravenous drug use for example, rather than sexual contact, have observed lower rates of reactive arthritis.[10]

Psoriasis and psoriatic arthritis tend to occur late in the course of HIV infection. They are often severe.

Human T-cell lymphotropic virus – 1 (HTLV-1) is a type C retrovirus (an RNA virus in the Oncovirinae subfamily) that infects millions of people worldwide, particularly in the Caribbean, southern Japan, South Africa, and South America. It is transmitted through ingestion of breast milk, sexual intercourse, and use of blood products. HTLV-1 infection is associated with Sjögren syndrome, as well as with the following diseases:

• Adult T-cell leukemia/non-Hodgkin lymphoma (lifetime risk, 5%) – These are commonly associated with hypercalcemia and skin involvement

• Chronic inflammatory syndromes (lifetime risk, 2%) These include a seronegative oligoarthritis or polyarthritis with tenosynovitis and nodules with fibrinoid necrosis; other syndromes include polymyositislike disease, dermatitis, uveitis, and transverse myelitis (known as tropical spastic paraparesis)

Other viruses

A number of other viruses have also been found to be capable of causing arthritis, including the following:

• Epstein-Barr virus – This infection is usually associated with polyarthralgia, but monoarthritis of the knee and ruptured Baker cysts may occur

• Varicella-zoster virus (VZV) – This infection in children rarely develops into pauciarticular arthritis[11]

• Mumps virus – In infected adults, this infection is associated with small or large joint synovitis that lasts for several weeks; arthritis may precede or follow parotitis by up to 4 weeks

• Adenovirus or coxsackieviruses A9, B2, B3, B4, and B6 – These infections have been associated with recurrent episodes of polyarthritis, pleuritis, myalgia, rash, pharyngitis, myocarditis, and leukocytosis

• Echovirus - This infection can be associated with polyarthritis, fever, and myalgias

• Herpes simplex virus (HSV) or cytomegalovirus (CMV) – Arthritis with these infections is rare; CMV arthritis has been reported in patients after bone marrow transplantation; vaccinia virus has been associated with postvaccination knee arthritis in only 2 reported cases

United States and international statistics

Although viral arthritis clearly is not uncommon in the United States, its exact incidence and prevalence are unknown and vary with the type of virus and the age range of specific population groups. It is estimated that approximately 2.7 million people are infected with HCV in the United States, and perhaps 0.01% of the population is infected with HBV.

Viral arthritis is known to occur worldwide, though its exact international incidence and prevalence are unknown,. The rate of HBV infection is higher in Asia (especially China [10% of the population]), the Mideast, and sub-Saharan Africa. HCV infection rates are higher in Africa and Asia.

Age-, sex-, and race-related demographics

Viral infection rates may be higher in adults than in children or the reverse, depending on the virus under consideration. HBV infection rates in childhood may be as high as 5% annually in some parts of the world. In adulthood, HBV is transmitted through sexual activity or needle exposures. Children are more susceptible to infection with parvovirus B19 than adults are, although they rarely experience arthritis. As many as 60% of adults have serologic evidence of past parvovirus B19 infection.

Parvovirus B19 infection is more common in women than in men. Whether HAV or HCV has a predilection for either sex is unknown. Viral arthritis has no recognized racial or ethnic predilection.

Viral arthritis is generally mild and self-limited, typically lasting no longer than a few weeks. There is no specific treatment for the arthritis; simple symptomatic measures (eg, analgesics, nonsteroidal anti-inflammatory drugs [NSAIDs], or, occasionally, low-dose prednisone) are sufficient.[12]

The major morbidity of viral arthritis is joint dysfunction. Mortality depends on the type of virus causing the arthritis and on the duration of infection.

Viral arthritis occurs during the viral prodrome, when the characteristic rash develops. In the United States, patients with the most common viral arthritides generally present with symmetrical small-joint involvement, though different patterns of joint and soft-tissue involvement occur with different viral infections. Many of the viruses that can cause arthritis have specific geographic niches (eg, HTLV-1 in Japan and the Caribbean), so a travel history will be important in some cases.

Physical findings in patients with viral arthritis vary substantially, depending on the type of virus causing the arthritis.

Parvovirus B19

Clinical features of arthritis associated with parvovirus B19 infection in children include the following:

• As many as 70% of patients are asymptomatic
• A few may have flulike symptoms (eg, fever, headache, sore throat, cough, anorexia, vomiting, diarrhea, or arthralgia)
• A bright red rash is typically noted, often characterized as having a “slapped-cheek” appearance (see the images below)
• Joint symptoms are rare (5-10%)
• Viral arthritis. Typical "slapped cheek" appearance. Courtesy of Brenda Moroz, MD, Montreal Children's Hospital.

  Viral arthritis. "Slapped cheeks" with typical reticulated erythema of arms. Courtesy of Brenda Moroz, MD, Montreal Children's Hospital.

Clinical features in adults include the following:

• Rash is rare

• Joint symptoms occur in as many as 60% of patients, with arthralgia noted more commonly than frank arthritis; arthralgia is usually self-limited and symmetrical and is noted in peripheral small joints, hands (ie, proximal interphalangeal and metacarpophalangeal joints), wrists, knees, and ankle joints, in association with prominent morning stiffness and swelling

• Several diseases may arise as a consequence of parvovirus B19 infection, such as erythema infectiosum (fifth disease), transient aplastic crisis (especially in patients with sickle cell disease, thalassemia, or HIV-induced anemia), and fetal hydrops in infected mothers

Rare clinical features include the following:

• Henoch-Schönlein purpura is rare but possible ^[13]
• Thrombotic thrombocytopenic purpura is unlikely but may be present
• Polyarteritis nodosa is rare
• Granulomatosis with polyangiitis (Wegener granulomatosis) is possible but rare

Hepatitis viruses

Clinical features of arthritis related to hepatitis B virus (HBV) infection include the following:

• Symmetric arthritis may be migratory or additive; with the hand and knee joints most commonly affected; significant morning stiffness and fusiform swelling are associated with HBV-induced arthritis

• Arthritis and urticaria may precede jaundice by days to weeks and may persist for several weeks after jaundice resolves

• Recurrent polyarthralgia or polyarthritis can occur in patients with chronic active hepatitis or chronic HBV viremia

• Polyarteritis nodosa may be associated with chronic HBV viremia

• Patients may have arthritis-dermatitis syndrome

• Nephropathy has been described

• Systemic necrotizing vasculitis is also a clinical feature

Clinical features of arthritis related to hepatitis C virus [HCV] infection include the following:

• A rapidly progressive acute arthralgia (but rarely arthritis) typically occurs in a rheumatoid distribution, affecting the hands, wrists, shoulders, knees, and hips

• Myalgia is common

• Essential mixed cryoglobulinemia (a triad of arthritis, palpable purpura, and cryoglobulinemia) is associated with HCV in most cases

• Necrotizing vasculitis with cryoglobulinemia is a clinical feature

• Essential mixed cryoglobulinemia type II or III is associated with more severe skin disease, such as Raynaud phenomenon, purpura, livedo reticularis, distal ulcers, gangrene, and peripheral neuropathy

• Sjögren syndrome has been described in numerous patients with HCV infection

• An association may exist between HCV infection and fibromyalgia

Rubella virus

Clinical features of arthritis associated with rubella virus infection (in both children and adults) include the following:

• Low-grade fever, malaise, and coryza are typical

• Rash (acute mild-to-severe viral exanthema [maculopapular rash]) appears first on the face, then the trunk and upper extremities, and finally on the lower extremities, sparing the palms and soles

• Significant lymphadenopathy (posterior cervical, postauricular, and occipital) may be noted

• Arthritis is usually sudden in onset, appearing 1 week before or after the rash; morning stiffness is symmetric and polyarticular in distribution (eg, fingers, knees, and wrists), brief in duration (lasting a few days to weeks), and without residua

• Arthritis similar to that occurring with natural infection may also develop within a few weeks of vaccination by attenuated rubella virus; the HPV77/DK12 strain is the most arthritogenic of the vaccine strains available in the United States; the currently used RA27/3 strain causes postvaccination joint symptoms in about 15% of recipients

In children, the following 2 syndromes may occur with either natural infection or vaccination:

• Arm syndrome – A brachial radiculoneuritis causes arm and hand pain and dysesthesias that worsen at night

• Catcher’s crouch syndrome – A lumbar radiculoneuropathy causes popliteal fossa pain when the child arises in the morning

Both syndromes occur 1-2 months after vaccination. The first episode may last up to 2 months, but recurrence is usually shorter in duration. Catcher’s crouch syndrome may recur for up to a year but causes no permanent damage.

Alphaviruses

Clinical features of arthritis associated with alphavirus infection include the following:

• Fever has been reported, with temperatures of 102.2-104°F (39-40°C)

• Arthritis or a migratory polyarthralgia of the small joints of the hands, wrists, elbows, knees, feet, and ankles occurs, along with stiffness and swelling; the arthritis is generally symmetric and polyarticular; in most alphavirus infections, joint symptoms resolve over 3-7 days, but they can persist for more than a year, albeit with no evidence of permanent joint damage

• Maculopapular rash may be itchy to some patients

Parvovirus B19

The incubation period for parvovirus B19 is 7-18 days, and the state of viremia lasts 5-6 days. The following studies are indicated:

• Complete blood count (CBC) to assess hemoglobin, neutrophils, and lymphocytes
• Immunoglobulin M (IgM) antibody titer – High levels may be noted 4-6 days after the initial viremia
• Viral B19 DNA by polymerase chain reaction (PCR)

The immunoglobulin G (IgG) antibody titer is of little diagnostic significance. Low-to-moderate titers for rheumatoid factor (RF), anti-DNA, antinuclear antibodies (ANAs), and anticardiolipin antibodies are possible in some patients.

Hepatitis viruses

The following tests may be ordered for hepatitis A virus (HAV):

• Bilirubin and transaminase levels – These are typically elevated
• IgM-specific anti-HAV

The following tests may be ordered for hepatitis B virus (HBV):

• Bilirubin and transaminase levels – These are commonly elevated but may be normal in the early stage of disease when arthritis is present
• Serum hepatitis B surface antigen (HBsAg), hepatitis B early antigen (HBeAg), anti-HBsAg IgM (indicative of acute infection), viral DNA, and PCR

The following tests may be ordered for hepatitis C virus (HCV):

• Bilirubin and transaminase levels – These are typically elevated, but normal transaminase levels do not exclude HCV infection
• Anti-HCV
• HCV-RNA by PCR
• Cryoglobulins and RF

Rubella virus

The following tests may be ordered for rubella virus:

• Anti–rubella virus IgM – This value peaks 8-21 days after symptoms, then wanes by 5 weeks
• Anti–rubella virus IgG – This value rises rapidly over a period of 1-3 weeks, and the rise is of long duration

Rubella virus has been isolated from lymphocytes and synovial fluid of patients who had vaccine-induced disease or who experienced rubella virus–associated arthritis years earlier.

Alphaviruses

Diagnosis of alphavirus infection is confirmed by specific serology results.

Retroviruses

In persons with HIV infection, laboratory abnormalities generally are common but nonspecific, including the following:

• Elevated levels of serum immunoglobulins
• Moderately elevated erythrocyte sedimentation rate (ESR)
• Circulating immune complexes
• Low-grade complement activation
• Low-titer ANA
• RF
• False-positive test result for syphilis and anticardiolipin antibodies
• Lupus anticoagulants
• Possible detection of CD8 ⁺ T cells and P-24 antigen in synovial fluid

Human T-lymphotropic virus (HTLV-1) infection is diagnosed on the basis of detection of antibodies by means of enzyme-linked immunosorbent assay (ELISA), with confirmation by Western blot and the observation of “flower cells” on the peripheral smear.

Radiologic findings in patients with viral arthritis depend on the specific condition. Most of the virus-associated arthropathies are nonerosive and show only soft-tissue swelling. However, with HIV-related seronegative or psoriatic-type arthropathy, erosions, ankylosis, narrowing of joint spaces, whittling, osteolytic lesions, periostitis, sacroiliac joint-space widening, and syndesmophyte formation can be seen.

Aspiration of the joint is useful to help rule out other conditions, such as crystal arthropathy or bacterial infection.

In general, viral arthritis is mild and requires only symptomatic treatment with analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs). Occasionally, a brief course of low-dose prednisone is used.

Surgical drainage is not indicated unless septic arthritis is considered likely. Most septic joints are managed effectively with a single surgical debridement. However, Hunter and colleagues reported that the risk factors for failure of a single surgical debridement included the following[14] :

• History of inflammatory arthropathy
• Involvement of a large joint
• Synovial fluid nucleated cell count of > 85.0 × 10 ⁹/L
• Infection with Staphylococcus aureus
• Diabetes mellitus

No dietary restrictions are necessary. Gentle mobilization may be initiated after a few days of rest.

In patients with rheumatoid arthritis (RA), the elevated risk of infection due to relative immunosuppression must be carefully assessed.[15] A better understanding of the cause of flareups would help predict patient responses to various therapies.[16]

Individuals with viral arthritis are usually treated in an outpatient setting. Order physical therapy as indicated. Follow-up care may be conducted by primary care physicians and rheumatologists. If the patient’s condition proves refractory, appropriate specialists can be consulted.

Preventive measures include the following:

• Vaccination
• Safe sex
• Clean food and drinking water
• Education

Parvovirus B19

Treatment of arthritis associated with parvovirus B19 infection is symptomatic, consisting primarily of administration of analgesics and NSAIDs. In severe cases, aspiration of fluid from the affected joint may relieve pain.

Hepatitis viruses

Treatment of arthritis associated with hepatitis A virus (HAV) is symptomatic, consisting primarily of administration of analgesics and NSAIDs. Prophylaxis for contacts is an important element of management.

No evidence indicates that early treatment of acute hepatitis B virus [HBV] infection with interferon alfa or antiviral agents decreases the rate of chronicity or speeds recovery. Most patients with acute icteric HBV infection recover without residual injury or chronic hepatitis. Management of acute HBV infection should be focused on avoidance of further hepatic injury and prophylaxis of contacts.

For hepatitis C virus (HCV) infection, treatment continues  to evolve rapidly. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C contains the most recent recommendations of the American Association for the Study of Liver Diseases (AASLD) and Infectious Diseases Society of America (ISDA).

Rubella virus

Treatment of arthritis associated with rubella virus infection is symptomatic, consisting primarily of administration of analgesics and NSAIDs. Some investigators have recommended giving corticosteroids at low to moderate doses to control symptoms and viremia.

Alphaviruses

Treatment of arthritis associated with alphavirus infection is symptomatic, involving the use of analgesics and NSAIDs, but aspirin should be avoided so as to prevent the development of a hemorrhagic component with alphavirus rashes. When NSAIDs are not effective, chloroquine phosphate 250 mg/day may be considered.

Chronic chikungunya arthritis shares several characteristics with rheumatoid arthritis such as persistent debilitating arthralgia and exacerbated inflammatory response. Because of these parallels, hydroxychloroquine (HCQ) and disease‐modifying antirheumatic drugs (DMARDs) such as methotrexate (MTX) and sulfasalazine have been evaluated in some peri‐epidemic clinical trials of treatments. However, these studies have produced conflicting outcomes and it remains unclear whether specific DMARDs are effective in treating chronic chikungunya arthritis.[17]

Retroviruses

For cases involving HIV infection, use currently recommended antiretroviral regimens, and treat symptoms with analgesics and NSAIDs. Administer sulfasalazine and methotrexate to patients who have conditions refractory to NSAID therapy. Prednisone, antimalarials, and other agents have been used successfully in patients with polymyositis, reactive arthritis, Sjögrenlike syndrome, psoriatic arthritis, and vasculitis.

Antiretroviral and prophylactic therapy, trimethoprim-sulfamethoxazole, and pentamidine help improve associated rheumatic symptoms. Intravenous immune globulin (IVIg), interleukin (IL)–12, IL-2, interferon gamma, or sargramostim may be effective in some HIV-infected patients with arthritis.

For human T-lymphotropic virus–1 (HTLV-1) infection, current treatment options are poor.

In general, patients can initially be seen by their family doctors. In patients who do not improve or in whom the treatment response is poor, the following practitioners may be consulted:

• Rheumatologists
• Hepatologists (if HBV or HCV infection is considered)
• Infectious disease specialists
• Immunologists

The goals of pharmacotherapy are to reduce morbidity and to prevent complications. Agents used to treat patients with viral arthritis include the following:

• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Antimalarials
• Immunoglobulins
• Interferons
• Corticosteroids
• Antineoplastic agents
• Other anti-inflammatory drugs
• Analgesics
• Antivirals
• Antibiotics

Class Summary

NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanisms of action are unknown, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may be present, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Naproxen (Anaprox, Naprelan, Aleve, Naprosyn)

Naproxen is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of cyclooxygenase, which is responsible for prostaglandin synthesis.

Ibuprofen (Motrin, Advil, Adapin, Caldolor)

Ibuprofen is the drug of choice for mild to moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis. Many doses are available, either with or without a prescription.

Ketoprofen

Ketoprofen is used for the relief of mild to moderate pain and inflammation. Small doses are indicated initially in patients with small body size, elderly patients, and persons with renal or liver disease. Doses of over 75 mg do not increase therapeutic effects. Administer high doses with caution, and closely observe the patient for response.

Flurbiprofen

Flurbiprofen may inhibit cyclooxygenase, thereby inhibiting prostaglandin biosynthesis. These effects may result in analgesic, antipyretic, and anti-inflammatory activities.

Diclofenac (Voltaren XR, Cataflam, Cambia)

This is one of a series of phenylacetic acids that has demonstrated anti-inflammatory and analgesic properties in pharmacological studies. It is believed to inhibit the enzyme cyclooxygenase, which is essential in the biosynthesis of prostaglandins. Diclofenac can cause hepatotoxicity; hence, liver enzymes should be monitored in the first 8 weeks of treatment. It is absorbed rapidly; metabolism occurs in the liver by demethylation, deacetylation, and glucuronide conjugation. The delayed-release, enteric-coated form is diclofenac sodium, and the immediate-release form is diclofenac potassium.

Tolmetin

Tolmetin inhibits prostaglandin synthesis by decreasing the activity of the enzyme cyclooxygenase, which, in turn, decreases the formation of prostaglandin precursors. The pediatric dosage is 20 mg/kg/d PO divided tid/qid initially, then 15-30 mg/kg/d, not to exceed 30 mg/kg/d.

Celecoxib (Celebrex)

Celecoxib inhibits primarily COX-2. Inhibition of COX-1 may contribute to NSAID GI toxicity. At therapeutic concentrations, COX-1 isoenzyme is not inhibited; thus, the incidence of GI toxicity, such as endoscopic peptic ulcers, bleeding ulcers, perforations, and obstructions may be decreased when compared with nonselective NSAIDs.

Seek the lowest dose for each patient. The adult dosage is 100-200 mg PO bid; the pediatric dosage has not been established for patients younger than 2 years, is 50 mg PO bid for patients 2 years or older whose weight ranges from 10 kg to no heavier than 25 kg, and is 100 mg PO bid for patients 2 years or older who weigh more than 25 kg.

Indomethacin (Indocin)

Indomethacin is used for relief of mild to moderate pain; it inhibits inflammatory reactions and pain by decreasing the activity of COX, which results in a decrease of prostaglandin synthesis.

Class Summary

Antimalarial agents are derivatives of 4-aminoquinoline and are active against various autoimmune disorders.

Hydroxychloroquine (Plaquenil)

Hydroxychloroquine inhibits chemotaxis of eosinophils and locomotion of neutrophils and impairs complement-dependent antigen-antibody reactions. Hydroxychloroquine sulfate 200 mg is equivalent to 155 mg hydroxychloroquine base and 250 mg chloroquine phosphate.

Class Summary

Immunoglobulins are used to improve clinical and immunologic aspects of the disease. They may decrease autoantibody production and increase solubilization and removal of immune complexes.

Immune globulin, intravenous (Carimune NF, Gammaplex, Octagam, Gammagard)

Neutralizes circulating myelin antibodies through antiidiotypic antibodies; down-regulates proinflammatory cytokines, including INF-gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells and augments suppressor T cells; blocks complement cascade; promotes remyelination; may increase CSF IgG (10%).Immune globulin, intravenous (Carimune NF, Gammaplex, Octagam, Gammagard)

Intravenous immune globulin (IVIg) neutralizes circulating myelin antibodies through anti-idiotypic antibodies; down-regulates proinflammatory cytokines, including interferon gamma; blocks Fc receptors on macrophages; suppresses inducer T and B cells while augmenting suppressor T cells; blocks the complement cascade; promotes remyelination; and may increase immunoglobulin G (IgG) in cerebrospinal fluid (CSF) (10%).

Class Summary

Interferons are naturally produced proteins with antiviral, antitumoral, and immunomodulatory actions. Interferons alfa, beta, and gamma may be given topically, systemically, and intralesionally.

Interferon alfa-2b (Intron A)

Interferon alfa-2b is a protein product manufactured by means of recombinant DNA technology. The mechanism of its antitumor activity is not clearly understood; however, direct antiproliferative effects against malignant cells and modulation of host immune response may play important roles.

Class Summary

Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli.

Prednisone

Prednisone is an immunosuppressant used for treatment of autoimmune disorders; it may decrease inflammation by reversing increased capillary permeability and suppressing polymorphonuclear leukocyte (PMN) activity. Prednisone stabilizes lysosomal membranes and suppresses lymphocyte and antibody production.

Prednisolone (Millipred, Orapred, Orapred ODT, Prelone)

Corticosteroids act as potent inhibitors of inflammation. They may cause profound and varied metabolic effects, particularly in relation to salt, water, and glucose tolerance, in addition to their modification of the immune response of the body. Alternative corticosteroids may be used in equivalent dosage.

Class Summary

These agents inhibit key factors responsible for deregulated cell proliferation.

Cyclophosphamide

Cyclophosphamide is an alkylating agent that depresses T- and B-cell function.

Methotrexate (Folex PFS, Rheumatrex)

Unknown mechanism of action in treatment of inflammatory reactions; may affect immune function. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness). Adjust dose gradually to attain satisfactory response.

Class Summary

Anti-inflammatory agents inhibit key factors responsible for inflammation.

Sulfasalazine (Azulfidine, EN-tabs)

Sulfasalazine is useful in the management of ulcerative colitis and acts locally in the colon to decrease the inflammatory response. It systemically inhibits prostaglandin synthesis.

Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who experience pain.

Acetaminophen (Aspirin-Free Anacin, FeverAll, Rapimed Junior, Tylenol)

Acetaminophen is the drug of choice for managing pain in patients who have documented hypersensitivity to aspirin or NSAIDs, who have upper gastrointestinal (GI) disease, or who are taking oral anticoagulants.

Class Summary

Nucleoside analogues are initially phosphorylated by viral thymidine kinase (TK) and eventually form a nucleoside triphosphate. These molecules inhibit herpes simplex virus (HSV) polymerase with 30-50 times the potency with which they inhibit human alpha-DNA polymerase.

Ribavirin (Rebetol, Virazole, Copegus)

Ribavirin is indicated for chronic hepatitis C virus (HCV) infection. It inhibits replication of RNA and DNA viruses; in addition, it inhibits initiation and elongation of RNA fragments, resulting in inhibition of viral protein synthesis.

Class Summary

Antibiotic therapy must cover all likely pathogens in the context of this clinical setting. Indications include Pneumocystis jiroveci pneumonia and HCV infection.

Pentamidine (Pentam-300, NebuPent)

Pentamidine inhibits the growth of protozoa by blocking oxidative phosphorylation and inhibiting incorporation of nucleic acids into RNA and DNA, causing inhibition of protein and phospholipid synthesis.

Trimethoprim-sulfamethoxazole (Septra DS, Bactrim, Bactrim DS)

Trimethoprim-sulfamethoxazole (TMP-SMZ) inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. The antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except for Pseudomonas aeruginosa.