Medication Summary
The goals of pharmacotherapy for reactive arthritis (ReA) are to reduce morbidity, to prevent joint damage, and to alleviate extra-articular disease. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstays of therapy for joint symptoms. Other types of agents used to treat ReA or its extra-articular manifestations include corticosteroids, antibiotics, and various disease-modifying antirheumatic drugs (DMARDs).
Nonsteroidal Anti-inflammatory Drugs (NSAIDs)
Class Summary
Several NSAIDs are available for relief of mild to moderate pain in ReA patients. They are similar with respect to effectiveness, though indomethacin may be more effective in the spondyloarthropathies. Cyclooxygenase (COX)-2–specific inhibitors can be used in patients at high risk for GI complications.
NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not fully known, but they may inhibit COX activity and prostaglandin synthesis. Other mechanisms, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions, may exist.
Aspirin and several NSAIDs are available for use in ReA patients and are comparably effective in treating symptoms.
Aspirin (Ascriptin, Bayer Aspirin, Bayer, Bufferin, Ecotrin Arthritis Strength)
Aspirin is a short-acting anti-inflammatory agent with rapid absorption in the proximal gastrointestinal (GI) tract. It is optimally effective only when stable serum levels of 150-250 µg/L are achieved after 3-5 days of treatment. Serum aspirin levels can be checked after 5-10 days of treatment. Maximal anti-inflammatory action is generally achieved within 2-4 weeks, with some further benefit occurring up to 3 months.
Ibuprofen (Motrin, Advil, NeoProfen, Addaprin)
Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.
Indomethacin (Indocin)
Indomethacin is the NSAID of choice in ReA; however, other NSAIDs are often effective as well. It is rapidly absorbed; metabolism occurs in the liver via demethylation, deacetylation, and glucuronide conjugation. Indomethacin inhibits prostaglandin synthesis; it is also a potent COX inhibitor, and this action may decrease local production of arachidonic acid–derived chemotactic factors for eosinophils present in sebum.
Naproxen (Naprosyn, Aleve, Naprelan)
Naproxen is used for relief of mild-to-moderate pain and is available in both short-acting and long-acting forms. It inhibits inflammatory reactions and pain by decreasing the activity of COX, which is responsible for prostaglandin synthesis.
Diclofenac (Voltaren, Cataflam XR, Zipsor, Cambia)
Diclofenac inhibits prostaglandin synthesis by decreasing COX activity, which, in turn, decreases formation of prostaglandin precursors.
Ketoprofen
Ketoprofen is used for relief of mild to moderate pain and inflammation. Small dosages are indicated initially in small patients, elderly patients, and patients with renal or liver disease. Doses higher than 75 mg do not increase the therapeutic effects. Administer high doses with caution, and closely observe the patient's response.
Corticosteroids
Class Summary
Corticosteroids have anti-inflammatory properties and cause profound and varied metabolic effects. They modify the body’s immune response to diverse stimuli. Topical corticosteroids are used for dermatologic manifestations of ReA, such as keratoderma blennorrhagicum and balanitis circinata (circinate balanitis). For ocular therapy, topical or subtenon injections of steroid have proven effective. Systemic steroids should only be used in cases of macular involvement and only for short periods.
Prednisone (Rayos)
Prednisone may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity the activity of polymorphonuclear leukocytes (PMNs).
Prednisolone acetate 1% (Pred Forte, Pred Mild, Omnipred)
Prednisolone acetate is used mainly for acute iritis. The best approach is to treat aggressively early in the course of the disease, then to gradually taper and discontinue the drug on the basis of the patient's clinical response.
Hydrocortisone valerate (CortAlo, TheraCort, U-Cort, Westcort)
Topical corticosteroids are adrenocorticosteroid derivatives suitable for application to skin or external mucous membranes; they have mineralocorticoid and glucocorticoid effects, resulting in a nonspecific anti-inflammatory activity.
Keratolytic Agents
Class Summary
These agents cause cornified epithelium to swell, soften, macerate, and then desquamate.
Salicylic acid topical (Calicylic, Aliclen, Keralyt, Salkera, Salvax)
Topical salicylic acid, by dissolving intercellular cement substance, produces desquamation of the horny layer of the skin, without affecting the structure of viable epidermis.
Antibiotics
Class Summary
Antibiotics may be used in ReA for antibacterial effects and for treatment of possible coexistent infection. Empiric antimicrobial therapy should cover all likely pathogens in the context of the clinical setting. Whenever feasible, antibiotic selection should be guided by blood culture sensitivity.
Tetracyclines are used to treat urethritis or cervicitis caused by chlamydial organisms. Some evidence shows that tetracycline treatment in chlamydia-induced ReA may reduce the duration, and perhaps the severity, of illness. Collagenase inhibitors have been used to treat early rheumatoid arthritis.
Erythromycin (EryPed 200, E.E.S. 400, Ery-Tab, PCE)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for treatment of infections caused by susceptible strains of microorganisms (eg, Mycoplasma pneumoniae and Staphylococcus, Streptococcus, and Chlamydia spp) and for prevention of corneal and conjunctival infections.
Erythromycin ophthalmic (Romycin, Ilotycin)
Erythromycin inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. It is indicated for the prevention of corneal and conjunctival infections.
Ciprofloxacin (Cipro, Cipro XR)
Ciprofloxacin is the drug of choice for obtaining improvement in clinical parameters (except joint involvement) in postenteric ReA. It is a bactericidal antibiotic that inhibits bacterial DNA synthesis and, consequently, growth by inhibiting DNA gyrase in susceptible organisms.
Tetracycline
Tetracycline is used to treat gram-positive and gram-negative infections, as well as mycoplasmal, chlamydial, and rickettsial infections. It inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits.
Doxycycline (Adoxa, Doryx, Vibramycin)
Doxycycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Minocycline (Minocin, Solodyn)
Minocycline is used to treat infections caused by susceptible gram-negative and gram-positive organisms, in addition to infections caused by susceptible Chlamydia, Rickettsia, and Mycoplasma organisms. It inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Azithromycin (Zithromax, Zmax)
Azithromycin is used to treat mild-to-moderate microbial infections.
Cefdinir
Cefdinir is a third-generation cephalosporin indicated for treatment of susceptible infections.
Aminosalicylic Acid Derivatives
Class Summary
Aminosalicylic acid derivatives are used to reduce inflammation when NSAIDs do not control arthritis or when inflammatory lesions of the intestinal mucosa are present.
Sulfasalazine (Azulfidine EN-tabs, Sulfazine, Sulfazine EC)
Sulfasalazine is used as a second-line therapy to treat ReA that is not controlled with NSAIDs alone. It is a conjugate of the salicylate 5-aminosalicylic acid (5-ASA) and the sulfonamide sulfapyridine (linked by an azo bond). Sulfasalazine is primarily excreted in the urine unchanged. Most of the 5-ASA remains in the colon and is not absorbed. Sulfasalazine acts locally to decrease the inflammatory response in the joints and systemically inhibits prostaglandin synthesis and folate metabolism.
Vitamins, Fat-Soluble
Class Summary
Vitamins are essential for normal synthesis of DNA and metabolism of proteins, carbohydrates, and fats.
Calcipotriene (Dovonex, Calcetrene, Sorilux)
Calcipotriene is a synthetic vitamin D-3 analogue that regulates skin-cell production and development. It is available as a 0.005% cream, ointment, or solution.
Antineoplastic Agents
Class Summary
Antineoplastic agents have immunosuppressive effects and inhibit cell growth and proliferation. They are used when the disease is aggressive and unremitting.
Azathioprine (Imuran, Azasan)
Azathioprine may be used alone or as a steroid-sparing agent. It antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. Azathioprine may decrease proliferation of immune cells, thereby reducing autoimmune activity. It is used more commonly for ReA and psoriasis. Thiopurine methyltransferase levels should be checked before azathioprine is used.
Methotrexate (Trexall, Rheumatrex)
Methotrexate is an antimetabolite that is indicated for the symptomatic control of severe ReA and severe, recalcitrant, disabling psoriasis. It is also used alone or in combination with other anticancer agents in the treatment of advanced mycosis fungoides and cancer of the head, neck, or lung, particularly those of the squamous-cell and small-cell types.
Antimalarials
Class Summary
Derivatives of 4-aminoquinoline are active against a variety of autoimmune disorders. They must be used with caution because hydroxychloroquine is known to be capable of exacerbating psoriasis. Because hydroxychloroquine is used for the joint involvement and not the skin involvement, it should probably be given only in conjunction with rheumatologic evaluation.
Hydroxychloroquine (Plaquenil)
It is not clear how hydroxychloroquine works. It is known to interfere with TLR signaling, inhibit chemotaxis of eosinophils neutrophils, and impair complement-dependent antigen-antibody reactions. A 200-mg quantity of hydroxychloroquine sulfate is equivalent to 155 mg of hydroxychloroquine base and 250 mg of chloroquine phosphate.
Retinoid-like Agents
Class Summary
Retinoids decrease the cohesiveness of abnormal hyperproliferative keratinocytes and may reduce the potential for malignant degeneration. They also modulate keratinocyte differentiation.
Isotretinoin (Absorica, Claravis, Myorisan, Zenatane)
Oral agent used to treat serious dermatologic conditions. It is a synthetic 13-cis isomer of the naturally occurring tretinoin (trans-retinoic acid), and both agents are structurally related to vitamin A. Isotretinoin alters the pattern of keratinization, reduces bacterial flora, and has an anti-inflammatory effect.
A US Food and Drug Administration (FDA)–mandated registry is now in place for all individuals prescribing, dispensing, or taking isotretinoin (see iPLEDGE). This registry aims to achieve further decreases in the risks of pregnancy and other unwanted and potentially dangerous adverse effects during a course of isotretinoin therapy.
Acitretin (Soriatane)
Acitretin is a retinoic acid analogue, similar to etretinate and isotretinoin. Etretinate is the main metabolite and has similar clinical effects. Acitretin's mechanism of action is unknown.
Tumor Necrosis Factor Blockers
Class Summary
Anti–tumor necrosis factor (TNF)–α therapy may be considered in refractory cases of ReA.
Infliximab (Remicade)
Infliximab is a chimeric IgG1κ monoclonal antibody that binds specifically to the soluble and transmembrane forms of TNF-α and inhibits the binding of TNF-α to its receptors.
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Balanitis circinata (circinate balanitis) in patient with reactive arthritis.
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Plaques on soles of patient with reactive arthritis.
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Painful erosions on fingers in patient with reactive arthritis.
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Plaques and erosions of tongue in patient with reactive arthritis.
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Radiograph of feet of 27-year-old man shows erosions in all left metatarsophalangeal (MTP) joints with subluxation and valgus deformity of most toes. Smaller erosions are also visible in fourth and fifth MTP joints of right foot.
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Lateral radiograph of foot reveals calcaneal spur and enthesitis.
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Radiograph of both hands shows small erosive changes in both first metacarpal heads associated with minimal subluxation. Bone density is normal.
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Radiography of pelvis reveals bilateral asymmetric sacroiliitis.
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Radiograph in 40-year-old man shows nonmarginal syndesmophytes predominantly in lower thoracic and upper lumbar spine.
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Swelling of right knee with effusion caused by arthritis. Image courtesy of Gun Phongsamart, MD.
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Remarkable tenderness of left sacroiliac joint caused by sacroiliitis. Image courtesy of Gun Phongsamart, MD.
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Balanitis circinata (circinate balanitis). Image courtesy of Gun Phongsamart, MD.
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Achilles tendinitis and swelling of retrocalcaneal bursa.
